Počet záznamů: 1

A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules

  1. 1.
    0349788 - BTO-N 2011 RIV US eng J - Článek v odborném periodiku
    Zhang, A.X. - Murelli, R.P. - Bařinka, Cyril - Michel, J. - Cocleaza, A. - Jorgensen, W.L. - Lubkowski, J. - Spiegel, D.A.
    A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules.
    Journal of the American Chemical Society. Roč. 132, č. 36 (2010), s. 12711-12716 ISSN 0002-7863
    Výzkumný záměr: CEZ:AV0Z50520701
    Klíčová slova: Prostate-specific membrane antigen * antibody recruiting molecules * Structure-activity relationship
    Kód oboru RIV: CE - Biochemie
    Impakt faktor: 9.019, rok: 2010

    Prostate specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase overexpressed in many forms of prostate cancer. We have recently disclosed a class of small molecules called ARM-Ps (antibody-recruiting molecule targeting prostate cancer) that are capable of enhancing antibody-mediated immune recognition of prostate cancer cells. Interestingly, we found ARM-Ps to exhibit extraordinarily high potencies toward PSMA, compared to previously reported inhibitors. Here, we report in-depth investigations which elucidate the origin of the observed affinity enhancement. These studies reveal a previously unreported arene-binding site on PSMA, which we believe participates in an aromatic stacking interaction with ARMs and drastically enhances small molecule binding affinity. These results provide critical insights into the design of PSMA-targeted small molecules for prostate cancer diagnosis and treatment.
    Trvalý link: http://hdl.handle.net/11104/0189938
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