title: SAR by oxime-containing peptide libraries: application to Tsg101 ligand optimization.
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.
authors.affiliation: Laboratory of Medicinal Chemistry, CCR, NCI-Frederick, Building 376 Boyles Street, Frederick, MD 21702, USA.
authors.forename: Fa
authors.initials: F
authors.lastname: Liu
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Stephen
authors.forename: Abdul A
authors.initials: AA
authors.lastname: Waheed
authors.forename: M Javad
authors.initials: MJ
authors.lastname: Aman
authors.forename: Eric O
authors.initials: EO
authors.lastname: Freed
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fisher
authors.forename: Terrence R
authors.initials: TR
authors.lastname: Burke
mesh_terms: D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D008024:Ligands; D010091:Oximes / Q000737:chemistry*; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*; D000099177:Tsg101 Protein
chemical_list: D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D008024:Ligands; D010091:Oximes; D019151:Peptide Library; D010455:Peptides; D014157:Transcription Factors; D000099177:Tsg101 Protein