SAR by oxime-containing peptide libraries: Application to Tsg101 ligand optimization
SAR by oxime-containing peptide libraries: Application to Tsg101 ligand optimization
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DOI：
10.1002/cbic.200800281
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发表时间：
2008-08-11
期刊：
影响因子：
3.2
通讯作者：
Burke, Terrence R., Jr.
中科院分区：
文献类型：
--
作者：
Liu, Fa;Stephen, Andrew G.;Burke, Terrence R., Jr.
HIV-1病毒组装需要病毒蛋白Gag-p6中的Pro-Thr-Ala-Pro（“PTAP”）基序与细胞内体分选因子Tsg101之间的直接相互作用。为了开发这种相互作用的竞争性抑制剂，基于固相肟形成后的应用进行了SAR研究，涉及在九聚物母体肽中顺序插入含氨氧基的残基，然后与醛库反应。通过这种方法，结合亲和力提高了大约 15-20 倍。
HIV-1 viral assembly requires a direct interaction between a Pro-Thr-Ala-Pro ("PTAP") motif in the viral protein Gag-p6 and the cellular endosomal sorting factor Tsg101. In an effort to develop competitive inhibitors of this interaction, an SAR study was conducted based on the application of post solid-phase oxime formation involving the sequential insertion of aminooxy-containing residues within a nonamer parent, peptide followed by reaction with libraries of aldehydes. Approximately 15-20-fold enhancement in binding affinity was achieved by this approach.