Robert Vince, PhD

Director, Center for Drug Design (CDD)

Robert Vince

Contact Info

vince001@umn.edu

Office Phone 612-624-9911

Office Address:
Nils Hasselmo Hall, Room 4-124
312 Church St SE
Minneapolis, MN 55455

Mailing Address:
MMC 204
312 Church St SE
Minneapolis, MN 55455

Administrative Assistant Name
Elizabeth Wolfson

Administrative Phone
612-624-2227

Administrative Fax Number
612-625-2633

PhD, University of Buffalo (Medicinal Chemistry), 1966

University of Buffalo, 1962

Summary

Dr. Robert Vince obtained his doctoral degree in medicinal chemistry in 1966 from the College of Pharmacy at SUNY Buffalo. In 1967 he joined the medicinal chemistry faculty at the University of Minnesota, where he continues to maintain his research program. His invention, the HIV drug, abacavir, was commercialized by GSK and has resulted in generation of revenue more than 600 million US dollars for the University of Minnesota.

In 2002, he established the Center for Drug Design within the Academic Health Center of the University of Minnesota. He has been honored for his work by a career development award from NIH (1972–1976), the 1979 University of Minnesota Scholar of the year award, and Certificate of Commendation by the Governor of Minnesota (1989). In recognition of achievements as an inventor, he was honored by the Minnesota Medical Alley, and Award of the New York Cayuga Community College (2002).

At University of Minnesota, he is recognized on ‘Scholars Walk and Wall of Discovery’ since 2006 and was inducted into the ‘Academy for Excellence in Health Research’ by the Academic Health Center of University of Minnesota (2009). He has also been inducted into the Medicinal Chemistry Hall of Fame (2007), by the American Chemical Society. He was awarded an honorary Doctorate of Science degree by his alma mater, SUNY–Buffalo (2010). The International Society for Nucleosides, Nucleotides and Nucleic Acids awarded him the 2010 Imbach Townsend Award. He was inducted in Minnesota Inventors Hall of Fame along with Nobel laureate Dr. Norman Borlaug (posth.), by the Minnesota Inventor’s Congress in 2010. 

He was inducted into the Minnesota Science and Technology Hall of fame in 2011.The significance of his many contributions to the University of Minnesota were recognized by President Kaler with the the presentation of the Inaugural Impact Award in December of 2014. He is also the latest awardee of the Antonin Holy Memorial Award (2016) conferred on him by the International Society of Antiviral Research.

Expertise

Antiviral drug design

Awards & Recognition

  • Antonin Holy Memorial Lecture Award (International Society for Antiviral Research), 2016
  • Received University of Minnesota’s Inaugural Impact Award, December 2014
  • Charles W. Hartman Memorial Lecture (University of Mississippi, MS), March 2014
  • David Chu Lectureship (University of Georgia, GA), 2013
  • Inducted into the Minnesota Science and Technology Hall of Fame, 2011
  • Inducted into Minnesota Inventors Hall of Fame along with Nobel laureate Dr. Norman Borlaug (posth.), by the Minnesota Inventor’s Congress, 2010
  • Received 2010 Imbach Townsend Award from the International Society for Nucleosides, Nucleotides and Nucleic Acids, 2010
  • Received Honorary Doctorate of Science Degree from SUNY Buffalo, 2010
  • Elected to the Academic Health Center Academy of Excellence in Health Research, 2009
  • Inducted into the American Chemical Society Medicinal Chemistry Hall of Fame, 2007
  • Recognized on ‘Scholars Walk and Wall of Discovery’ at the University of Minnesota, 2006
  • Selected by the University to meet President George W. Bush, 2002
  • Honored by the Minnesota Medical Alley and received the Award of the New York Cayuga Community College, 2002
  • Certificate of Commendation by the Governor, Rudy Perpich, of Minnesota, 1989
  • Who's Who in America, 1980
  • University of Minnesota Scholar of the Year Award, 1979
  • Career Development Award from National Cancer Institute, 1972-1976
  • Outstanding Educators of America, 1974
  • Outstanding Young Men of America, 1967

Professional Associations

Research

Research Summary/Interests

Our laboratory researches new anti-viral drugs and focuses in particular on developing new treatments for Acquired Immune Deficiency Syndrome (AIDS). The virus which causes AIDS relies on several unique viral proteins which do not occur naturally in the human body. Our goal is to design novel molecules which block the chemical reactions carried out by these viral proteins, thereby preventing the virus from growing in the human body.

One of the viral proteins, reverse transcriptase, assembles genetic building blocks to make copies of the viral genetic material. We designed modified genetic building blocks (such as carbovir, shown on the right) which interfere with reverse transcriptase without harming the proteins responsible for maintaining the human body's genetic material. This research led to the development of the commercially available anti-HIV drug Ziagen®. We are currently investigating possible new drugs targeting the reverse transcriptase, protease, and integrase enzymes of HIV. Other areas of focus for our anti-viral programs are Herpes, Hepatitis B, and Hepatitis C.

Cancer typically involves damage to the human body's genetic material. Several anti-cancer projects are ongoing based on our extensive history of creating modified genetic building blocks. In fact, the development of our anti-viral program and the successful design of the AIDS drug was a spin off of our anti-cancer drug program. Since most of the successful anti-tumor drugs are modified genetic building blocks, we continue to work in this area for the discovery of new cancer drugs.

We have also recently initiated a program to study Vitamin C in cancer chemoprevention and treatment. Vitamin C is an antioxidant, but we have found some additional interesting properties of Vitamin C that have potential for anti-cancer and cancer chemopreventive applications. We are studying these properties and will use our results to redesign the molecule into a more stable and effective potential drug.

Antiviral Drugs

Following the identification of a human retrovirus (HIV) as the etiologic agent of the Acquired Immunodeficiency Syndrome (AIDS), an intense effort was made to identify drugs for the treatment of this debilitating, lethal disease. Ongoing research in our laboratory deals with the development of anti-viral agents and has focused on the design of anti-HIV drugs. In response to the initial project for a very large-scale anti-HIV drug screening and AIDS drug development program at the National Cancer Institute, researchers in our lab developed a series of carbocyclic nucleoside analogs. These compounds have design features compatible with action as DNA chain terminators and are structurally analogous to natural nucleosides, the only difference being that a methylene group replaces the oxygen atom of the carbohydrate ring.

The studies showed that these analogs, called carbovirs, which lack a labile glycosidic bond, are stable to hydrolytic cleavage while retaining the therapeutically useful interaction with enzymes involved in DNA and RNA synthesis. As a result, several of the carbocyclic nucleosides inhibited the infectivity and replication of HIV in T-cells and led to the development of the commercially available anti-HIV drug, Ziagen®.

Other approaches to the design of anti-AIDS drugs at the Center for Drug Design include:

  • Create a new protease inhibitor to block the ability of the virus to produce essential proteins
  • Construct integrase enzyme inhibitors designed to prevent the virus from integrating its own DNA into the DNA of human cells
  • Other areas of focus for our anti-viral programs are Herpes, Hepatitis B, and Hepatitis C

Cancer Therapy

Several anti-cancer projects are ongoing based on our extensive history of nucleoside analog production. In fact, the development of our anti-viral program and the successful design of the AIDS drug, was a spin off of our anti-cancer drug program. Since most of the successful anti-tumor drugs are nucleoside analogs, we continue to work in this area for the discovery of new cancer drugs.

We have recently initiated a program to study Vitamin C in cancer chemoprevention and treatment. The Vitamin C molecule has important and interesting anti-oxidant properties (free radical elimination) but is vulnerable to metabolism and elimination from the body. We have found some interesting unrelated properties of Vitamin C that have potential for anti-cancer and cancer chemopreventive applications. We are studying these properties and will use our results to redesign the molecule into a more stable and effective potential drug.

Patents

22. Vince, R.; Raza, A.; Dreis, C. (University of Minnesota, USA) Preparation of thymine-based sunless tanning compounds and composition. WO 2015003095 A1 20150108; SciFinder Scholar 2015:34969

21. Vince, R.; Raza, A.; Dreis, C. (University of Minnesota, USA). Preparation of open-chained or fused 1,1'-alkylene-bis-uracil derivatives useful for skin UV-protection. WO 2014059350 A1 20140417 - See more at: 2014:616445

20. Vince, R. (University of Minnesota, USA). Thymine derivatives useful in preventing or repairing skin damage through up-regulation of key DNA and their preparation. WO 2013106728 A1; SciFinder Scholar 2013:1122487.

19. Vince R.; More, S. S. (University of Minnesota, USA). Hyperspectral imaging for early detection of Alzheimer's disease. WO 2013086516; SciFinder Scholar 2013:928416.

ahCCDD2 - Content - Image - Hyperspectral Scheme - 763px

18. Vince, R.; More, S. S. (University of Minnesota, USA). Glutathione analogs for treating neurodegenerative disorders. WO 2013009647; SciFinder Scholar 2013:87205.

17. Vince, R.; Vartak, A. P. (University of Minnesota, USA). Method for preparation of 5-substituted pyrimidines. WO 2012128965; SciFinder Scholar 2012:1402235.

16. Wang, Z.; Geraghty, R. J.; Vince, R.; Tang, J. (University of Minnesota, USA). N-Hydroxypyrimidine-2,4-diones as inhibitors of HIV and HCV and their preparation. WO 20111005; SciFinder Scholar 2012:533369.

15. Patterson, S.; Vince, R.; Nagasawa, H. (University of Minnesota, USA). Preparation of amino salts of sulfanegen as cyanide antidotes. WO 20110422.; SciFinder Scholar 2011:1373796.

14. Pankiewicz, K.; Chen, L.; Vince, R. (Regents of the University of Minnesota, USA). Preparation of ureas and related compounds having dual inhibitory activity for IMPDH/HDAC. WO 20080730.; SciFinder Scholar 2009:139320.

13. Nagasawa, H. T.; Goon, D. J. W.; Crankshaw, D. L.; Vince, R. (Regents of the University of Minnesota, USA; Department of Veterans Affairs). Therapeutic methods, compositions, and compounds that can release mercaptopyruvate for use in the treatment of cyanide poisoning. WO 20070628.; SciFinder Scholar 2008:43123.

12. Vince, R.; Peterson, M. L.; Lackey, J. W.; Mook, R. A., Jr.; Partridge, J. J.(Glaxo, Inc., USA). Preparation of (-)-carbovir. WO 19910404.; SciFinder Scholar 1992:59910.

11. Vince, R.; Hua, M. (University of Minnesota, USA). Preparation of optically active carbocyclic purine 2',3'-didehydro-2',3'-dideoxynucleosides and their analogs as antiviral and antitumor agents. US 19881205.; SciFinder Scholar 1991:43491.

10. Vince, R.; Hua, M. (University of Minnesota, USA). Preparation of optically active isomers of dideoxycarbocyclic nucleosides as antiviral and antitumor agents. US 19881223.; SciFinder Scholar 1991:102708.

9. Vince, R.; Shannon, W. M. (University of Minnesota, USA; Southern Research Institute). Preparation of purine nucleosides as antiviral agents and pharmaceutical compositions containing them. EP 19890609.; SciFinder Scholar 1990:217469.

8. Vince, R.; Hua, M.; Myers, P. L.; Storer, R. (University of Minnesota, USA). Preparation and testing of antitumor and antiviral carbocyclic dideoxynucleosides and pharmaceutical compositions containing them. DE 19890119.; SciFinder Scholar 1990:56589.

7. Vince, R. (University of Minnesota, USA). Preparation of carbocyclic analogs of xylofuranosylpurines as antiviral and antitumor agents. EP 19860909.; SciFinder Scholar 1987:423661.

6. Vince, R. (University of Minnesota, USA). 3-Ethoxypropionate esters of cyclaradine. US 19840730.; SciFinder Scholar 1987:18995.

5. Vince, R. (University of Minnesota, USA). Adenosine deaminase resistant antiviral purine arabinonucleosides. US 19810911.; SciFinder Scholar 1983:438790.

4. Vince, R. (University of Minnesota, USA). Adenosine deaminase resistant antiviral purine nucleosides. US 19790105.; SciFinder Scholar 1981:498246.

3. Vince, R. (University of Minnesota, USA). Adenine nucleoside derivatives and pharmaceutical compositions containing them. EP 19810619.; SciFinder Scholar 1982:181575.

2. Vince, R. (University of Minnesota, USA). Adenosine deaminase-resistant antiviral purine nucleosides. US 19770209.; SciFinder Scholar 1979:168938.

1. Vince, R. (University of Minnesota). (±)-9-?-(3-?-Amino-2?-hydroxy cyclopentyl)-6-substituted-purines and derivatives. US 19720126.; SciFinder Scholar 1975:58074.

Publications

  •  More, S.S.; Nugent, J.; Vartak, A. P.; Nye, S. M.; Vince, R. Hepatoprotective Effect of y-Glutathione in a Murine Model of Acetaminophen-Induced Liver Toxicity. Chem. Res. Toxicol. 2017, Ahead of Print.
  • More, S. S.; Beach, J. M.; Vince, R. Early Detection of Amyloidopathy in Alzheimer's Mice by Hyperspectral Endoscopy. Invest. Ophthalmol. Visual Sc. 2016, 57, 3231-3238 (Abstract).
  • Patterson, S. E.; Moeller, B.t; Nagasawa, H. T.; Vince, R.; Crankshaw, D. L.; Briggs, J.; Stutelberg, M. W.; Vinnakota, C. V.; Logue, B. A. Development of sulfanegen for mass cyanide casualties. Ann. N. Y. Acad. Sci. 2016, 1374 (1), 202-209.
  • Wezena, C. A.; Urscher, M.; Vince, R.; More, S. S.; Deponte, M. Hemolytic and Antimalarial Effects of Tight-binding Glyoxalase 1 Inhibitors on the Host-parasite Unit of Erythrocytes Infected with Plasmodium falciparum. Redox Biol. 2016, 8, 348-353.
  • Nugent, J. S.; Vince, R.; Raza, A. Topical Acyclothymidine Dinucleosides (aTds) Promote Non-UV-Mediated Endogenous Defense Mechanisms in Guinea Pig Skin J. Invest. Dermatol. 2015, 135, 1687-1689.
  • More, S. S.; Vince, R. Hyperspectral Imaging Signatures Detect Amyloidopathy in Alzheimer's Mouse Retina Well before Onset of Cognitive Decline. ACS Chem. Neurosci. 2015, 6, 306-315. (Abstract)

aHCCDD2 - Content - Image - More Hyperspectral Image 1

  • Felczak, K.; Vince, R.; Pankiewicz, K. W. NAD-Based Inhibitors with Anticancer Potential Bioorg. Med. Chem. Lett. 2014, 24, 332-336. (Abstract)
  • Raza, A.; Ericson, M. E.; Nugent, J. S.; Dreis, C. D.; Vince, R. A Bio-Mimetic Approach to DNA Photoprotection J. Invest. Dermatol. 2014, 134, 559-562. (Abstract)
  • Patterson, S. E.; Monteil, A. R.; Cohen, J. F.; Crankshaw, D. L.; Vince, R.; Nagasawa, H. T. Cyanide Antidotes for Mass Casualties: Water-Soluble Salts of the Dithiane (Sulfanegen) from 3-Mercaptopyruvate for Intramuscular Administration J. Med. Chem. 2013, 56, 1346-1349. (Abstract)
  • Raza, A.; Dreis, C. D.; Vince, R. Photoprotection of DNA (in vitro) by Acyclothymidine Dinucleosides Bioorg. Med. Chem. Lett. 2013, 23, 620-623. (Abstract)
  • More, S. S.; Vartak, A. P.; Vince, R. Restoration of Glyoxalase Enzyme Activity Precludes Cognitive Dysfunction in a Mouse Model of Alzheimer's Disease ACS Chem. Neurosci. 2012, 4, 330-338. (Abstract)

ahCCDD2 - Content - Image -Glyoxalase Scheme - 735px

  • More, S. S.; Vartak, A. P.; Vince, R. The Butter Flavorant, Diacetyl, Exacerbates ?-Amyloid Cytotoxicity Chem. Res. Toxicol. 2012, 25, 2083-2091. (Abstract)
  • Urscher, M.; More, S. S.; Alisch, R.; Vince, R.; Deponte, M. Tight-binding Inhibitors Efficiently Inactivate both Reaction Centers of Monomeric Plasmodium falciparum Glyoxalase 1. FEBS J. 2012, 279, 2568-2578. (Abstract)
  • Singh, R.; Vince, R. 2–Azabicyclo[2.2.1]hept–5–en–3–one: Chemical Profile of a Versatile Synthetic Building Block and its Impact on the Development of Therapeutics. Chem. Rev. 2012, 112, 4642-4686. (Abstract)

ahCCDD2 - Content - Image - VLactam Scheme - 735px

  • Chen, Y.-L.; Zacharias, J.; Vince, R.; Geraghty, R. J.; Wang, Z. C-6 Aryl Substituted 4-Quinolone-3-carboxylic Acids as Inhibitors of Hepatitis C Virus. Bioorg. Med. Chem. 2012, 20, 4790-4800.(Abstract)
  • Belani, K. G.; Singh, H.; Beebe, D. S.; George, P.; Patterson, S. E.; Nagasawa, H. T.; Vince, R. Cyanide Toxicity in Juvenile Pigs and Its Reversal by a New Prodrug, Sulfanegen Sodium. Anesth Analg. 2012, 114, 956-961. (Abstract)
  • More, S. S.; Raza, A.; Vince, R. The Butter Flavorant, Diacetyl, Forms a Covalent Adduct with 2-Deoxyguanosine, Uncoils DNA, and Leads to Cell Death. J. Agric. Food Chem. 2012, 60, 3311-3317. (Abstract)
  • More, S. S.; Vince, R.  Potential of a ?-Glutamyl-Transpeptidase-Stable Glutathione Analogue against Amyloid-? Toxicity. ACS Chem. Neurosci. 2012, 3, 204-212. (Abstract)
  • Chen, Y. L.; Tang, J.; Kessler, M. J.; Sham, Y. Y.; Vince, R.; Geraghty, R. J.; Wang, Z. The Design, Synthesis and Biological Evaluations of C-6 or C-7 Substituted 2-Hydroxylisoquinoline-1,3-diones as Inhibitors of Hepatitis C Virus. Bioorg. Med. Chem. 2012, 20, 467-479. (Abstract)
  • Urscher, M.; More Swati, S.; Alisch, R.; Vince, R.; Deponte, M., Tight-binding inhibitors efficiently inactivate both reaction centers of monomeric Plasmodium falciparum glyoxalase 1. The FEBS journal 2012.
  • Raza, A.; Vince, R.  Dehydroascorbic Acid Adducts of Guanosine Residues: Possible Biological Implications. ChemBioChem 2011, 12, 1015-1017.(Abstract)
  • Tang, J.; Maddali, K.; Dreis, C. D.; Sham, Y. Y.; Vince, R.; Pommier, P.; Wang, Z. 6-Benzoyl-3-hydroxypyrimidine-2,4-diones as Dual Inhibitors of HIV Reverse Transcriptase and Integrase. Bioorg. Med. Chem. Lett. 2011, 21, 2400-2402. (Abstract)
  • Tang, J.; Maddali, K.; Sham, Y. Y.; Vince, R.; Pommier, Y.; Wang, Z. 3-Hydroxypyrimidine-2,4-diones as a New Inhibitor Scaffold of HIV Integrase. J. Med. Chem. 2011, 54, 2282-2292. (Abstract)
  • Felczak, K.; Chen, L.; Wilson, D.; Williams, J.; Vince, R.; Petrelli, R.; Jayaram, H. N.; Kusumanchi, P.; Kumar, M.; Pankiewicz, K. P.  Cofactor-type Inhibitors of Inosine Monophosphate Dehydrogenase via Modular Approach: Targeting the Pyrophosphate Binding Sub-domain. Bioorg. Med. Chem. 2011, 19, 1594-1605. (Abstract)
  • Tang, J.; Maddali, K.; Dreis, C. D.; Sham, Y. Y.; Vince, R.; Pommier, Y.; Wang, Z. N-3 Hydroxylation of Pymimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase. ACS Medicinal Chem. Lett. 2011, 2, 63-67. (Abstract)
  • Wang, Z.; Tang, J.; Salomon, C. E.; Dreis, C. D.; Vince, R., Pharmacophore and structure-activity relationships of integrase inhibition within a dual inhibitor scaffold of HIV reverse transcriptase and integrase. Bioorg. Med. Chem. 2010, 18, 4202-4211.
  • Lu, D.; Sham, Y. Y.; Vince, R., Design, asymmetric synthesis, and evaluation of pseudosymmetric sulfoximine inhibitors against HIV-1 protease. Bioorg. Med. Chem. 2010, 18, 2037-2048.
  • More, S. S.; Vince, R., Inhibition of Glyoxalase I: The First Low-Nanomolar Tight-Binding Inhibitors. J. Med. Chem. 2009, 52, 4650-4656.
  • Wang, Z.; Vince, R., Synthesis of pyrimidine and quinolone conjugates as a scaffold for dual inhibitors of HIV reverse transcriptase and integrase. Bioorg. Med. Chem. Lett. 2008, 18, 1293-1296.
  • Wang, Z.; Vince, R., Design and synthesis of dual inhibitors of HIV reverse transcriptase and integrase: Introducing a diketoacid functionality into delavirdine. Bioorg. Med. Chem. 2008, 16, 3587-3595.
  • Vince, R., A brief history of the development of Ziagen. Chemtracts 2008, 21, 127-134.
  • Raza, A.; Sham, Y. Y.; Vince, R., Design and synthesis of sulfoximine based inhibitors for HIV-1 protease. Bioorg. Med. Chem. Lett. 2008, 18, 5406-5410.
  • More, S. S.; Vince, R., Design, synthesis and biological evaluation of glutathione peptidomimetics as components of anti-parkinson prodrugs. J. Med. Chem. 2008, 51, 4581-4588.
  • Lu, D.; Vince, R., Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality. [Erratum to document cited in CA147:541559]. Bioorg. Med. Chem. Lett. 2008, 18, 2228.
  • Wang, Z.; Bennett, E. M.; Wilson, D. J.; Salomon, C.; Vince, R., Rationally Designed Dual Inhibitors of HIV Reverse Transcriptase and Integrase. J. Med. Chem. 2007, 50, 3416-3419.
  • Pham, P.-T.; Vince, R., Carbovir-related compounds and phosphonate analogues. Phosphorus, Sulfur Silicon Relat. Elem. 2007, 182, 779-791.
  • Nagasawa, H. T.; Goon, D. J. W.; Crankshaw, D. L.; Vince, R.; Patterson, S. E., Novel, Orally Effective Cyanide Antidotes. J. Med. Chem. 2007, 50, 6462-6464.
  • More, S. S.; Vince, R., Design, synthesis, and binding studies of bidentate Zn-chelating peptidic inhibitors of glyoxalase-I. Bioorg. Med. Chem. Lett. 2007, 17, 3793-3797.
  • Lu, D.; Vince, R., Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality. Bioorg. Med. Chem. Lett. 2007, 17, 5614-5619.
  • Tang, Y.; Muthyala, R.; Vince, R., Synthesis and biological evaluation of carboacyclic nucleosides with (Z) and (E)-9-[4,4-bis(hydroxymethyl)]-2-butenyl side chain. Bioorg. Med. Chem. 2006, 14, 5866-5875.
  • More, S. S.; Vince, R., A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I. Bioorg. Med. Chem. Lett. 2006, 16, 6039-6042.
  • Li, X.; Vince, R., Conformationally restrained carbazolone-containing ?,?-diketo acids as inhibitors of HIV integrase. Bioorg. Med. Chem. 2006, 14, 2942-2955.
  • Li, X.; Vince, R., Synthesis and biological evaluation of purine derivatives incorporating metal chelating ligands as HIV integrase inhibitors. Bioorg. Med. Chem. 2006, 14, 5742-5755.
  • Vince, R.; Hua, M., Synthesis of carbovir and abacavir from a carbocyclic precursor. Current protocols in nucleic acid chemistry / edited by Serge L. Beaucage ... [et al.] 2006, Chapter 14, Unit 14 4.
  • Dorr, D. R. Q.; Vince, R., Synthesis and biological evaluation of endocyclic 2',3'-didehydro-2',3'-dideoxymethanocarba adenosine. Nucleosides, Nucleotides Nucleic Acids 2002, 21, 665-680.
  • Bhushan, R. G.; Vince, R., Synthesis of conformationally restricted 2',3'-exo-Methylene carbocyclic nucleosides built on a bicyclo[3.1.0]hexane template. Bioorg. Med. Chem. 2002, 10, 2325-2333.
  • Parker, W. B.; Shaddix, S. C.; Rose, L. M.; Pham, P. T.; Hua, M.; Vince, R., Metabolism of O6-propyl and N6-propyl-carbovir in CEM cells. Nucleosides, Nucleotides Nucleic Acids 2000, 19, 795-804.
  • Vince, R.; Brownell, J.; Akella, L. B., Synthesis and activity of ?-(L-?-azaglutamyl)-S-(p-bromobenzyl)-L-cysteinylglycine: a metabolically stable inhibitor of glyoxalase I. Bioorg. Med. Chem. Lett. 1999, 9, 853-856.
  • Antle, V. D.; Donat, N.; Hua, M.; Liao, P.-L.; Vince, R.; Caperelli, C. A., Substrate specificity of human glycinamide ribonucleotide transformylase. Arch. Biochem. Biophys. 1999, 370, 231-235.
  • Katagiri, N.; Kokufuda, H.; Makino, M.; Vince, R.; Kaneko, C., Synthesis of nucleoside and related compounds. 42. Deamination of cyclaradine by adenosine deaminase under high pressure. Nucleosides Nucleotides 1998, 17, 81-89.
  • Parker, W. B.; Shaddix, S. C.; Vince, R.; Bennett, L. L., Jr., Lack of mitochondrial toxicity in CEM cells treated with carbovir. Antiviral Res. 1997, 34, 131-136.
  • Katagiri, N.; Kokufuda, H.; Makino, M.; Matsuhashi, Y.; Kaneko, C.; Vince, R., A highly efficient synthesis of cyclaradine and its behavior towards adenosine deaminase. Nucleic Acids Symp. Ser. 1997, 37, 3-4.
  • Vince, R.; Hua, M.; Caperelli, C. A., Phosphonate analogs of carbocyclic phosphoribosylamine and carbocyclic glycinamide ribonucleotide. Nucleosides Nucleotides 1996, 15, 1711-1718.
  • Konkel, M. J.; Vince, R., Cyclohexenyl nucleosides. Synthesis of cis-4-(9H-purin-9-yl)-2-cyclohexenylcarbinols. Tetrahedron 1996, 52, 799-808.
  • Konkel, M. J.; Vince, R., Cyclohexenyl nucleosides: synthesis and biological activity of trans-3-(purin-9-yl)-4-cyclohexenylcarbinols. Tetrahedron 1996, 52, 8969-8978.
  • Konkel, M. J.; Vince, R., Palladium-Catalyzed Allylic Coupling of 1,2,3-Triazolo[4,5-d]pyrimidines (8-Azapurines). J. Org. Chem. 1996, 61, 6199-6204.
  • Antle, V. D.; Liu, D.; McKellar, B. R.; Caperelli, C. A.; Hua, M.; Vince, R., Substrate specificity of glycinamide ribonucleotide transformylase from chicken liver. J. Biol. Chem. 1996, 271, 6045-9.
  • Antle, V. D.; Liu, D.; McKellar, B. R.; Caperelli, C. A.; Hua, M.; Vince, R., Substrate specificity of glycinamide ribonucleotide synthetase from chicken liver. J. Biol. Chem. 1996, 271, 8192-5.
  • Akella, L. B.; Vince, R., Palladium-catalyzed synthesis of cis-2-[4-(9H-purin-9-yl)-2-cyclopenten-1-yl]ethanol analogs. Tetrahedron 1996, 52, 2789-94.
  • Akella, L. B.; Vince, R., Enantioselective synthesis of 2-[5-(9H-purin-9-yl)-2-cyclopenten-1-yl]-ethanol analogs as potential antiviral agents. Tetrahedron 1996, 52, 8407-8412.
  • Wen, Y.-D.; Remmel, R. P.; Pham, P. T.; Vince, R.; Zimmerman, C. L., Comparative brain exposure to (-)-carbovir after (-)-carbovir or (-)-6-aminocarbovir intravenous infusion in rats. Pharm. Res. 1995, 12, 911-15.
  • Vince, R.; Pham, P. T., The synthesis and biological evaluation of sulfamoyl nucleosides related to carbovir and AZT. Nucleosides Nucleotides 1995, 14, 2051-60.
  • Vince, R.; Kilama, J.; Pham, P. T.; Beers, S. A., 6-Substituted derivatives of carbovir: anti-HIV activity. Nucleosides Nucleotides 1995, 14, 1703-8.
  • Vince, R.; Brownell, J.; Beers, S. A., 6-Deoxycarbovir: a xanthine oxidase activated prodrug of carbovir. Nucleosides Nucleotides 1995, 14, 39-44.
  • Konkel, M. J.; Vince, R., Synthesis and biological activity of cyclohexenyl nucleosides. cis-5-(9H-Purin-9-yl)-3-cyclohexenyl carbinols and their 8-azapurinyl analogs. Nucleosides Nucleotides 1995, 14, 2061-77.
  • Parker, W. B.; Shaddix, S. C.; Bowdon, B. J.; Rose, L. M.; Vince, R.; Shannon, W. M.; Bennett, L. L., Jr., Metabolism of carbovir, a potent inhibitor of human immunodeficiency virus type 1, and its effects on cellular metabolism. Antimicrob. Agents Chemother. 1993, 37, 1004-9.
  • Zimmerman, C. L.; Remmel, R. P.; Ibrahim, S. S.; Beers, S. A.; Vince, R., Pharmacokinetic evaluation of (-)-6-aminocarbovir as a prodrug for (-)-carbovir in rats. Drug Metab. Dispos. 1992, 20, 47-51.
  • Peterson, E. M.; Brownell, J.; Vince, R., Synthesis and biological evaluation of 5'-sulfamoylated purinyl carbocyclic nucleosides. J. Med. Chem. 1992, 35, 3991-4000.
  • Vince, R., Synthesis and anti-HIV activity of carbovir and related carbocyclic nucleosides. Nucleic Acids Symp. Ser. 1991, 25, 193-4.
  • Peterson, M. L.; Vince, R., Synthesis and biological evaluation of 4-purinylpyrrolidine nucleosides. J. Med. Chem. 1991, 34, 2787-97.
  • Parker, W. B.; White, E. L.; Shaddix, S. C.; Ross, L. J.; Buckheit, R. W., Jr.; Germany, J. M.; Secrist, J. A., III; Vince, R.; Shannon, W. M., Mechanism of inhibition of human immunodeficiency virus type 1 reverse transcriptase and human DNA polymerases ?, ?, and ? by the 5'-triphosphates of carbovir, 3'-azido-3'-deoxythymidine, 2',3'-dideoxyguanosine, and 3'-deoxythymidine. A novel RNA template for the evaluation of antiretroviral drugs. J. Biol. Chem. 1991, 266, 1754-62.
  • Vince, R.; Hua, M., Synthesis and anti-HIV activity of carbocyclic 2',3'-didehydro-2',3'-dideoxy 2,6-disubstituted purine nucleosides. J. Med. Chem. 1990, 33, 17-21.
  • Vince, R.; Brownell, J., Resolution of racemic carbovir and selective inhibition of human immunodeficiency virus by the (-) enantiomer. Biochem. Biophys. Res. Commun. 1990, 168, 912-16.
  • Peterson, M. L.; Vince, R., Synthesis and biological evaluation of carbocyclic analogs of lyxofuranosides of 2-amino-6-substituted purines and 2-amino-6-substituted-8-azapurines. J. Med. Chem. 1990, 33, 1214-19.
  • Bondoc, L. L., Jr.; Shannon, W. M.; Secrist, J. A., III; Vince, R.; Fridland, A., Metabolism of the carbocyclic nucleoside analog carbovir, an inhibitor of human immunodeficiency virus, in human lymphoid cells. Biochemistry 1990, 29, 9839-43.
  • Yeom, Y. H.; Remmel, R. P.; Huang, S. H.; Hua, M.; Vince, R.; Zimmerman, C. L., Pharmacokinetics and bioavailability of carbovir, a carbocyclic nucleoside active against human immunodeficiency virus, in rats. Antimicrob. Agents Chemother. 1989, 33, 171-5.
  • White, E. L.; Parker, W. B.; Macy, L. J.; Shaddix, S. C.; McCaleb, G.; Secrist, J. A., III; Vince, R.; Shannon, W. M., Comparison of the effect of Carbovir, AZT, and dideoxynucleoside triphosphates on the activity of human immunodeficiency virus reverse transcriptase and selected human polymerases. Biochem. Biophys. Res. Commun. 1989, 161, 393-8.
  • Remmel, R. P.; Yeom, Y. H.; Hua, M.; Vince, R.; Zimmerman, C. L., Liquid chromatographic assay of carbovir, a carbocyclic nucleoside active against human immunodeficiency virus. J. Chromatogr., Biomed. App. 1989, 489, 323-31.
  • Vince, R.; Hua, M.; Brownell, J.; Daluge, S.; Lee, F.; Shannon, W. M.; Lavelle, G. C.; Qualls, J.; Weislow, O. S.; et al., Potent and selective activity of a new carbocyclic nucleoside analog (carbovir: NSC 614846) against human immunodeficiency virus in vitro. Biochem. Biophys. Res. Commun. 1988, 156, 1046-53.
  • Vince, R.; Turakhia, R. H.; Shannon, W. M.; Arnett, G., Synthesis and antiviral activity of carbocyclic analogs of xylofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines. J. Med. Chem. 1987, 30, 2026-30.
  • Hua, M.; Korkowski, P. M.; Vince, R., Synthesis and biological evaluation of acyclic neplanocin analogs. J. Med. Chem. 1987, 30, 198-200.
  • Vince, R.; Daluge, S.; Brownell, J., Carbocyclic purmocyin: synthesis and inhibition of protein biosynthesis. J. Med. Chem. 1986, 29, 2400-3.
  • Dunham, E. W.; Vince, R., Hypotensive and renal vasodilator effects of carbocyclic adenosine (aristeromycin) in anesthetized spontaneously hypertensive rats. J. Pharmacol. Exp. Ther. 1986, 238, 954-9.
  • Vince, R.; Shannon, W. M.; Nagabhushan, T. L., Carbocyclic arabinofuranosyladenine (cyclaradine): synthesis and antiviral efficacy. Int. Congr. Ser.1985, 667, 77-9.
  • Vince, R.; Brownell, J.; Daluge, S., Carbocyclic analogs of xylofuranosylpurine nucleosides. Synthesis and antitumor activity. J. Med. Chem. 1984, 27, 1358-60.
  • McFarlan, S. C.; Vince, R., Inhibition of peptidyltransferase and possible mode of action of a dipeptidyl chloramphenicol analog. Biochem. Biophys. Res. Commun. 1984, 122, 748-54.
  • Vince, R.; Daluge, S.; Lee, H.; Shannon, W. M.; Arnett, G.; Schafer, T. W.; Nagabhushan, T. L.; Reichert, P.; Tsai, H., Carbocyclic arabinofuranosyladenine (cyclaradine): efficacy against genital herpes in guinea pigs. Science (Washington, DC, United States) 1983, 221, 1405-6.
  • Shannon, W. M.; Westbrook, L.; Arnett, G.; Daluge, S.; Lee, H.; Vince, R., Comparison of the efficacy of vidarabine, its carbocyclic analog (cyclaradine), and cyclaradine-5'-methoxyacetate in the treatment of herpes simplex virus type 1 encephalitis in mice. Antimicrob. Agents Chemother. 1983, 24, 538-43.
  • Vince, R.; Lee, H.; Narang, A. S.; Shirota, F. N., 5'-Chloropuromycin. Inhibition of protein synthesis and antitrypanosomal activity. J. Med. Chem. 1981,24, 1511-14.
  • Lee, H.; Fong, K.-L.; Vince, R., Puromycin analogs. Effect of aryl-substituted puromycin analogs on the ribosomal peptidyltransferase reaction. J. Med. Chem. 1981, 24, 304-8.
  • Cermak, R. C.; Vince, R., (±)-4?-Amino-2?,3?-dihydroxy-1?-cyclopentanemethanol hydrochloride. Carbocyclic ribofuranosylamine for the synthesis of carbocyclic nucleosides. Tetrahedron Letters 1981, 22, 2331-2
  • Vince, R.; Daluge, S., Facile synthesis of carbocyclic lyxo- and ribonucleosides. J. Org. Chem. 1980, 45, 531-3.
  • Lee, H.; Vince, R., Carbocyclic analogs of arabinosylpurine nucleosides. J. Pharm. Sc. 1980, 69, 1019-21.
  • Wienen, B.; Ehrlich, R.; Stoeffler-Meilicke, M.; Stoeffler, G.; Smith, I.; Weiss, D.; Vince, R.; Pestka, S., Ribosomal protein alterations in thiostrepton- and micrococcin-resistant mutants of Bacillus subtilis. J. Biol. Chem. 1979, 254, 8031-41.
  • Broom, A. D.; Amarnath, V.; Vince, R.; Brownell, J., Poly(2-fluoroadenylic acid). The role of basicity in the stabilization of complementary helixes. Biochim. Biophys. Acta, Nucleic Acids Protein Synth. 1979, 563, 508-17.
  • Vince, R.; Fong, K.-L. L., Peptidyl transferase substrate activity and inhibition of protein biosynthesis by a hydrophilic-aminoacyl analog of puromycin. Biochem. Biophys. Res. Commun. 1978, 81, 559-64.
  • Vince, R.; Brownell, J.; Fong, K.-L. L., Photoaffinity labeling of the ribosomal peptidyl transferase site with synthetic puromycin analogs. Biochemistry 1978, 17, 5489-93.
  • Lee, C. K.; Vince, R., Effect of sparsomycin analogs on the puromycin-peptidyl transferase reaction on ribosomes. J. Med. Chem. 1978, 21, 176-9.
  • Fong, K.-L. L.; Vince, R., Peptidyl transferase substrate specificity with nonaromatic aminoacyl analogs of puromycin. J. Med. Chem. 1978, 21, 792-5.
  • Daluge, S.; Vince, R., Synthesis of carbocyclic aminonucleosides. J. Org. Chem. 1978, 43, 2311-20.
  • Brandt-Rauf, P.; Vince, R.; LeMahieu, R.; Pestka, S., Fluorescent assay for estimating the binding of erythromycin derivatives to ribosomes. Antimicrob. Agents Chemother. 1978, 14, 88-94.
  • Vince, R.; Daluge, S., Carbocyclic arabinosyladenine, an adenosine deaminase resistant antiviral agent. J. Med. Chem. 1977, 20, 612-13.
  • Vince, R.; Daluge, S., Synthesis of cyclohexyl carbocyclic puromycin and its inhibition of protein synthesis. J. Med. Chem. 1977, 20, 930-4.
  • Vince, R.; Brownell, J.; Lee, C. K., Inhibition of protein biosynthesis: the first active sparsomycin analog. Biochem. Biophys. Res. Commun. 1977, 75, 563-7.
  • Narang, A. S.; Vince, R., 1,2,4-Triazole amino nucleosides. 1-?-D-3'-amino-3'-deoxyribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides. J. Med. Chem. 1977, 20, 1684-7.
  • Lyon, P. A.; Vince, R., Synthesis and kinetic evaluation of S- and N-substituted cysteinylglycines as inhibitors of glyoxalase I. J. Med. Chem. 1977, 20, 77-80.
  • Langlois, R.; Cantor, C. R.; Vince, R.; Pestka, S., Interaction between the erythromycin and chloramphenicol binding sites on the Escherichia coli ribosome. Biochemistry 1977, 16, 2349-56.
  • Vince, R.; Weiss, D.; Pestka, S., Binding of N-substituted erythromycylamines to ribosomes. Antimicrob. Agents Chemother. 1976, 9, 131-6.
  • Vince, R.; Weiss, D.; Gordon, J.; Howard, G.; Smith, I.; Pestka, S., Binding of thiostrepton to ribosomes from thiostrepton-sensitive and -resistant Bacillus subtilis strains. Antimicrob. Agents Chemother. 1976, 9, 665-7.
  • Vince, R.; Almquist, R. G.; Ritter, C. L.; Shirota, F. N.; Nagasawa, H. T., An active puromycin analog derived from a non-nephrotoxic aminonucleoside. Life Sci. 1976, 18, 345-9.
  • Pestka, S.; Weiss, D.; Vince, R.; Wienen, B.; Stoeffler, G.; Smith, I., Thiostrepton-resistant mutants of Bacillus subtilis: localization of resistance to the 50S subunit. Mol. Gen. Genet. 1976, 144, 235-41.
  • Pestka, S.; Weiss, D.; Vince, R., Partition of ribosomes in two-polymer aqueous phase systems. Anal. Biochem. 1976, 71, 137-42.
  • Pestka, S.; Vince, R.; LeMahieu, R.; Weiss, F.; Fern, L.; Unowsky, J., Induction of erythromycin resistance in Staphylococcus aureus by erythromycin derivatives. Antimicrob. Agents Chemother. 1976, 9, 128-30.
  • Langlois, R.; Lee, C. C.; Cantor, C. R.; Vince, R.; Pestka, S., The distance between two functionally significant regions of the 50 S Escherichia coli ribosome: the erythromycin binding site and proteins L7/L12. J. Mol. Biol. 1976, 106, 297-313.
  • Daluge, S.; Vince, R., A synthetic route to carbocyclic aminonucleosides. Tetrahedron Lett. 1976, 3005-8.
  • Vince, R.; Almquist, R. G.; Ritter, C. L.; Daluge, S., Chloramphenicol binding site with analogs of chloramphenicol and puromycin. Antimicrob. Agents Chemother. 1975, 8, 439-43.
  • Duquette, P. H.; Ritter, C. L.; Vince, R., Puromycin analogs. Ribosomal binding and peptidyl transferase substrate activity of a carbocyclic analog of 8-azapuromycin. Biochemistry 1974, 13, 4855-9.
  • Vince, R.; Daluge, S. Puromycin Analogs. Ribosomal Binding with Diastereomeric Carbocyclic Puromycin Analogs. J. Med. Chem. 1974, 17, 578-583.
  • Vince, R.; Almquist, R. G. Formation of Arabino Nucleosides from 3-acetamido-1,2-di-O-acetyl-3,5-dideoxy-D-ribofuranose During the Fusion Synthesis. Carbohydr. Res. 1974, 36, 214-218.
  • Vince, R.; Wolf, M.;Sanford, C. Glutaryl-S-(p-bromobenzyl)-L-cysteinylglycine. Metabolically Stable Inhibitor of Glyoxalase I. J. Med. Chem. 1973, 16, 951-953.
  • Vince, R.; Isakson, R. G. Acyclic Puromycin Analog. 6-Dimethylamino-9-[2-hydroxy-3-(p-methoxyphenyl-L-alanylamino)propyl]purine. J. Med. Chem. 1973, 16, 37-40.
  • Pestka, S.; Vince, R.; Daluge, S.; Harris, R. Effect of Puromycin Analogs and Other Agents on Peptidyl-Puromycin Synthesis on Polyribosomes. Antimicrob. Agents Chemother. 1973, 4, 37-43.
  • Almquist, R. G.; Vince, R. Puromycin Analogs. Synthesis and Biological Activity of 5'-Deoxypuromycin and Its Aminonucleoside, 6-Dimethylamino-9-(3'-amino-3',5'-dideoxy-?-D-ribofuranosyl)purine. J. Med. Chem. 1973, 16, 1396.
  • Vince, R.; Daluge, S.; Palm, M. Inhibition of in Vitro Protein Synthesis by a Carbocyclic Puromycin Analog. Biochem. Biophys. Res. Commun. 1972, 46, 866-70.
  • Daluge, S.; Vince, R. Synthesis and Antimicrobial Activity of a Carbocyclic Puromycin Analog. 6-Dimethylamino-9-[R-[2R-hydroxy-3R-(p-methoxyphenyl-L-alanylamino)]cyclopentyl]purine. J. Med. Chem. 1972, 15, 171-177.
  • Vince, R.; Daluge, S.; Wadd, W. B. Inhibition of Glyoxalase I by S-Substituted Glutathiones. J. Med. Chem. 1971, 14, 402-4.
  • Vince, R.; Daluge, S. Glyoxalase Inhibitors. A Possible Approach to Anticancer Agents. J. Med. Chem. 1971, 14, 35-7.
  • Schaeffer, H. J.; Gurwara, S.; Vince, R.; Bittner, S. Novel Substrate of Adenosine Deaminase. J. Med. Chem. 1971, 14, 367-9.
  • Vince, R.; Wadd, W. B. Glyoxalase Inhibitors as Potential Anticancer Agents. Biochem. Biophys. Res. Commun. 1969, 35, 593-8.
  • Vince, R.; Donovan, J. Nucleoside Analogs. Synthesis of 6-(6-amino-9-purinyl)-1,5-anhydro-6-deoxy-L-allitol. J. Med. Chem. 1969, 12, 175-6.
  • Schaeffer, H. J.; Vince, R. Enzyme Inhibitors. XIX. Synthesis of Some 1-Hydroxy-2-Hydroxymethyl-4-(6)Substituted-9-Purinyl)Cyclohexanes as Nucleoside Analogs. J. Med. Chem. 1968, 11, 15-20.
  • Schaeffer, H. J.; Vince, R. Enzyme Inhibitors. XVIII. The stereoselectivity of inhibition of adenosine deaminase by DL-, D-, and L-9-(2-hydroxypropyl)adenine. J. Med. Chem. 1967, 10, 689-91.
  • Schaeffer, H. J.; Vince, R. Enzyme Inhibitors VI. Studies on the Bulk Tolerance of Adenosine Deaminase for 6-Substituted Amino-9-(3-Hydroxypropyl)Purines. J. Med. Chem. 1965, 8, 33-35.
  • Schaeffer, H. J.; Vince, R. Enzyme Inhibitors. X. A Reinvestigation of the Alkylation of 6-Chloropurine by 3-Bromo-1-Propanol. J. Med. Chem. 1965, 8, 710-712.
  • Schaeffer, H. H.; Vogel, D.; Vince, R. Enzyme Inhibitors. Viii. Studies on the Mode of Binding of Some 6-Substituted 9-(Hydroxyalkyl)Purines to Adenosine Deaminase. J. Med. Chem. 1965, 8, 502-506.
  • Schaeffer, H. J.; Vince, R. Intramolecular Reactions of Some Cyclic ?-Diketones. J. Org. Chem. 1962, 27, 4502-4505.

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