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SAR by Oxime‐Containing Peptide Libraries: Application to Tsg101 Ligand Optimization
Author(s) -
Liu Fa,
Stephen Andrew G.,
Waheed Abdul A.,
Aman M. Javad,
Freed Eric O.,
Fisher Robert J.,
Burke Terrence R.
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800281
Subject(s) - oxime , peptide , chemistry , combinatorial chemistry , tsg101 , human immunodeficiency virus (hiv) , peptide library , ligand (biochemistry) , endosome , stereochemistry , computational biology , biochemistry , peptide sequence , biology , virology , receptor , microrna , microvesicles , gene
Abstract 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.