title: Application of a novel design paradigm to generate general nonpeptide combinatorial templates mimicking beta-turns: synthesis of ligands for melanocortin receptors.
abstract: We report the further application of a novel approach to template and ligand design by the synthesis of agonists of the melanocortin receptor. This design method uses the conserved structural data from the three-dimensional conformations of beta-turn peptides to design rigid nonpeptide templates that mimic the orientation of the main chain C-alpha atoms in a peptide beta-turn. We report details on a new synthesis of derivatives of template 1 that are useful for the synthesis of exploratory libraries. The utility of this technique is further exemplified by several iterative rounds of high-throughput synthesis and screening, which result in new partially optimized nonpeptide agonists for several melanocortin receptors.
authors: ChemBridge Research Labs, Inc., ChemBridge Corporation, 16981 Via Tazon, San Diego, California 92127, USA. thomas.webb@stjude.org
authors: Thomas R
authors: TR
authors: Webb
authors: Luyong
authors: L
authors: Jiang
authors: Sergey
authors: S
authors: Sviridov
authors: Ruben E
authors: RE
authors: Venegas
authors: Anna V
authors: AV
authors: Vlaskina
authors: Douglas
authors: D
authors: McGrath
authors: John
authors: J
authors: Tucker
authors: Jian
authors: J
authors: Wang
authors: Alain
authors: A
authors: Deschenes
authors: Rongshi
authors: R
authors: Li
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003412:Cricetulus; D030562:Databases, Protein; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010455:Peptides; D044101:Receptors, Melanocortin