• 10173 Citations
1968 …2024

Research output per year

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Personal profile

Research Interests

The research in Professor Silverman’s group can be summarized as investigations of the molecular mechanisms of action, rational design, and syntheses of potential medicinal agents. The primary focus is basic research into central nervous system disorders, including Parkinson’s disease, cerebral palsy, amyotrophic lateral sclerosis, addiction, and epilepsy. Other therapeutic areas include cancer (melanoma and hepatocellular carcinoma), lysosomal storage diseases, such as Gaucher’s disease, and bacterial infection. Numerous drugs are known to function as specific inhibitors of particular enzymes. For some enzyme targets, where potent reversible inhibitors are desired, computer modeling based on X-ray crystal structures initiates the research (high-throughput screening also may be used). For enzyme targets where inactivators are desired and when little is known about the enzyme’s molecular mechanism of action, chemical model studies are designed to determine reasonable nonenzymatic pathways applicable to the enzyme. For those enzymes, mechanism-based inactivators are designed and synthesized and inactivation mechanisms investigated. The enzymes are isolated from either mammalian tissue or from overexpressed cells containing recombinant enzymes. Collaborations are developed in X-ray crystallography and preclinical studies.

Education/Academic qualification

Organic Chemistry, PhD, Harvard University

… → 1974

Chemistry, BS, Pennsylvania State University

… → 1968

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Grants

  • Research Output

    A Remarkable Difference That One Fluorine Atom Confers on the Mechanisms of Inactivation of Human Ornithine Aminotransferase by Two Cyclohexene Analogues of γ-Aminobutyric Acid

    Zhu, W., Doubleday, P. F., Catlin, D. S., Weerawarna, P. M., Butrin, A., Shen, S., Wawrzak, Z., Kelleher, N. L., Liu, D. & Silverman, R. B., Mar 11 2020, In : Journal of the American Chemical Society. 142, 10, p. 4892-4903 12 p.

    Research output: Contribution to journalArticle

  • Inducible nitric oxide synthase: Regulation, structure, and inhibition

    Cinelli, M. A., Do, H. T., Miley, G. P. & Silverman, R. B., Jan 1 2020, In : Medicinal Research Reviews. 40, 1, p. 158-189 32 p.

    Research output: Contribution to journalReview article

  • 11 Scopus citations

    Mechanism-Based Design of 3-Amino-4-Halocyclopentenecarboxylic Acids as Inactivators of GABA Aminotransferase

    Shen, S., Doubleday, P. F., Weerawarna, P. M., Zhu, W., Kelleher, N. L. & Silverman, R. B., Jan 1 2020, (Accepted/In press) In : ACS Medicinal Chemistry Letters.

    Research output: Contribution to journalArticle

  • 3 Scopus citations

    Conversion of Quinazoline Modulators from Inhibitors to Activators of β-Glucocerebrosidase

    Zheng, J., Jeon, S., Jiang, W., Burbulla, L. F., Ysselstein, D., Oevel, K., Krainc, D. & Silverman, R. B., Feb 14 2019, In : Journal of Medicinal Chemistry. 62, 3, p. 1218-1230 13 p.

    Research output: Contribution to journalArticle

  • 4 Scopus citations