Robert Vince, PhD

Academic Health Center

College of Pharmacy

Department of Medicinal Chemistry

Institute for Molecular Virology

Center for Drug Design (CDD)

Bio

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. Recently, he has been inducted into the Minnesota Science and Technology Hall of Fame (2011).

Expertise

Antiviral drug design

Awards & Recognition

• Antonin Holy Memorial Lecture Award (International Society for Antiviral Research), 2016
• Received University of Minnesota OVPR’s 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 Minnesota Science & 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 AHC Academy of Excellence in Health Research, 2009
• Inducted into ACS Medicinal Chemistry Hall of Fame, 2007
• Recognized on ‘Scholars Walk and Wall of Discovery’ at the University of Minnesota, 2006
• Selected by The White House 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

Research Summary

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.

• 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.
• 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)
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• 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)
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• 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)
• 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
• 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.
• Vince R.; More, S. S. (University of Minnesota, USA). Hyperspectral imaging for early detection of Alzheimer's disease. WO 2013086516; SciFinder Scholar 2013:928416.
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• Vince, R.; More, S. S. (University of Minnesota, USA). Glutathione analogs for treating neurodegenerative disorders. WO 2013009647; SciFinder Scholar 2013:87205.
• Vince, R.; Vartak, A. P. (University of Minnesota, USA). Method for preparation of 5-substituted pyrimidines. WO