• Login
    View Item 
    •   Shocker Open Access Repository Home
    • Fairmount College of Liberal Arts and Sciences
    • Chemistry
    • CHEM Faculty Scholarship
    • CHEM Faculty Publications
    • View Item
    •   Shocker Open Access Repository Home
    • Fairmount College of Liberal Arts and Sciences
    • Chemistry
    • CHEM Faculty Scholarship
    • CHEM Faculty Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Utilization of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold in the design of potent inhibitors of serine proteases: SAR studies using carboxylates

    Date
    2000-05-01
    Author
    Kuang, Rongze
    Epp, Jeffrey B.
    Ruan, Sumei
    Chong, Lee S.
    Venkataraman, Radhika
    Tu, Juan
    He, Shu
    Truong, Tien M.
    Groutas, William C.
    Metadata
    Show full item record
    Citation
    Bioorganic & medicinal chemistry. 2000 May; 8(5): 1005-16.
    Abstract
    A series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds has been synthesized and the inhibitory profile of these compounds toward human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3) was then determined. Most of the compounds were found to be potent, time-dependent inhibitors of elastase, with some of the compounds exhibiting k(inact)/K1 values as high as 4,928,300 M(-1) s(-1). The inhibitory potency of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide platform was found to be influenced by both the pKa and the inherent structure of the leaving group. Proper selection of the primary specificity group (R(I)) was found to lead to selective inhibition of HLE over Cat G, however, those compounds that inhibited HLE also inhibited PR 3, albeit less efficiently. The predictable mode of binding of these compounds suggests that, among closely-related serine proteases, highly selective inhibitors of a particular serine protease can be fashioned by exploiting subtle differences in their S' subsites. This study has also demonstrated that the degradative action of elastase on elastin can be abrogated in the presence of inhibitor 17.
    Description
    Full text of this article is not available in SOAR.
    URI
    http://hdl.handle.net/10057/4347
    Collections
    • CHEM Faculty Publications

    Browse

    All of Shocker Open Access RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsBy TypeThis CollectionBy Issue DateAuthorsTitlesSubjectsBy Type

    My Account

    LoginRegister

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    DSpace software copyright © 2002-2021  DuraSpace
    Contact Us | Send Feedback
    DSpace Express is a service operated by 
    Atmire NV