Synthesis and Screening of Linear and Cyclic Oligocarbamate Libraries. Discovery of High Affinity Ligands for GPIIb/IIIa
详细信息 查看全文
- 作者：Charles Y. Cho ; R. Scott Youngquist ; Sari J. Paikoff ; Maureen H. Beresini ; Andrea R. Hebert ; Lea T. Berleau ; Corey W. Liu ; David E. Wemmer ; Thomas Keough ; and Peter G. Schultz
- 刊名：Journal of the American Chemical Society
- 出版年：1998
- 出版时间：August 12, 1998
- 年：1998
- 卷：120
- 期：31
- 页码：7706 - 7718
- 全文大小：331K
- 年卷期：v.120,no.31(August 12, 1998)
- ISSN：1520-5126
文摘
Synthetic methodology has been developed for the generation of large, diverse libraries of "unnatural"carbamate oligomers using the "one bead, one peptide" method. Using a pool of 27 structurally and functionallydiverse monomers, one acyclic and two cyclic libraries were synthesized and screened for binding to theintegrin GPIIb/IIIa. Several classes of oligocarbamate ligands for GPIIb/IIIa were discovered, and two cyclicligands have activities that are within a factor of 3 of kistrin, a snake venom protein that effectively inhibitsplatelet aggregation. Preliminary pharmacokinetic characterization was performed on a linear oligocarbamateligand, which was cleared from plasma with a half-life of 3.6 min.