https://scholars.lib.ntu.edu.tw/handle/123456789/454775
標題: | Development and evaluation of novel phosphotyrosine mimetic inhibitors targeting the Src homology 2 domain of signaling lymphocytic activation molecule (SLAM) associated protein | 作者: | Chu C.-Y. Chang C.-P. Chou Y.-T. Handoko, Hu Y.-L. Lo L.-C. JING-JER LIN |
公開日期: | 2013 | 卷: | 56 | 期: | 7 | 起(迄)頁: | 2841-2849 | 來源出版物: | Journal of Medicinal Chemistry | 摘要: | Specific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-containing counterparts play significant role in cellular protein tyrosine kinase (PTK) signaling pathways. The SH2 domain inhibitors could potentially serve as drug candidates in treating human diseases. Here we have incorporated a novel phosphotyrosine mimetic, which is an unusual amino acid carrying a cyclosaligenyl (cycloSal) phosphodiester moiety, into dipeptides to investigate the inhibitory effect on SH2 domain-containing proteins. A plate-based assay was also established to screen for inhibitors that disrupt the interaction between a phosphopeptide of SLAM (signaling lymphocytic activation molecule) and its interacting protein SAP (SLAM-associated protein). We identified a number of inhibitors with IC50 values in the range of 17-35 μM, implying that the cycloSal phosphodiester-carrying amino acid could mimic the phosphotyrosyl residue. Our results also raise the possibility of integrating the newly developed phosphotyrosine mimetic moiety into inhibitors designed for other SH2 domain-containing proteins. ? 2013 American Chemical Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876237519&doi=10.1021%2fjm301610q&partnerID=40&md5=c9f12350a58449139ed36a52ebbe5845 https://scholars.lib.ntu.edu.tw/handle/123456789/454775 |
ISSN: | 0022-2623 | DOI: | 10.1021/jm301610q | SDG/關鍵字: | CD150 antigen; phosphotyrosine; phosphotyrosine derivative; signaling lymphocyte activation molecule associated protein; unclassified drug; article; binding assay; chemical modification; controlled study; drug mechanism; drug protein binding; drug screening; drug structure; drug synthesis; drug targeting; IC 50; molecular docking; nonhuman; protein protein interaction; signal transduction; Src homology domain; Binding Sites; Intracellular Signaling Peptides and Proteins; Models, Molecular; Molecular Mimicry; Phosphotyrosine; src Homology Domains |
顯示於: | 生物化學暨分子生物學科研究所 |
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