Liu Fa, Stephen Andrew G, Waheed Abdul A, Aman M Javad, Freed Eric O, Fisher Robert J, Burke Terrence R
Laboratory of Medicinal Chemistry, CCR, NCI-Frederick, Building 376 Boyles Street, Frederick, MD 21702, USA.
Chembiochem. 2008 Aug 11;9(12):2000-4. doi: 10.1002/cbic.200800281.
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.
HIV-1病毒组装需要病毒蛋白Gag-p6中的脯氨酸-苏氨酸-丙氨酸-脯氨酸（“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，基于后固相肟形成的应用进行了一项构效关系（SAR）研究，该方法包括在一个九聚体母体肽中依次插入含氨氧基的残基，然后与醛类文库反应。通过这种方法，结合亲和力提高了约15至20倍。
