title: Synthesis and screening of stereochemically diverse combinatorial libraries of peptide tertiary amides.
abstract: Large combinatorial libraries of N-substituted peptides would be an attractive source of protein ligands, because these compounds are known to be conformationally constrained, whereas standard peptides or peptoids are conformationally mobile. Here, we report an efficient submonomer solid-phase synthetic route to these compounds and demonstrate that it can be used to create high quality libraries. A model screening experiment and analysis of the hits indicates that the rigidity afforded by the stereocenters is critical for high affinity binding.
authors.affiliation: Department of Chemistry, Scripps Florida, Jupiter, FL 33458, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Thomas
authors.initials: T
authors.lastname: Kodadek
mesh_terms: D000577:Amides / Q000032:analysis* / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D008968:Molecular Conformation; D034444:Peptoids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000577:Amides; D008024:Ligands; D034444:Peptoids; D054852:Small Molecule Libraries