title: Exploration of structure-activity relationships at the two C-terminal residues of potent 11mer Glucagon-Like Peptide-1 receptor agonist peptides via parallel synthesis.
abstract: We report the identification of potent agonists of the Glucagon-Like Peptide-1 receptor (GLP-1R) via evaluation of two positional scanning libraries and a two-dimensional focused library, synthesized in part on SynPhase Lanterns. These compounds are 11 amino acid peptides containing several unnatural amino acids, including (in particular) analogs of biphenylalanine (Bip) at the two C-terminal positions. Typical activities of the most potent peptides in this class are in the picomolar range in an in vitro functional assay using human GLP-1 receptor.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Tasir S
authors.initials: TS
authors.lastname: Haque
authors.forename: Rogelio L
authors.initials: RL
authors.lastname: Martinez
authors.forename: Ving G
authors.initials: VG
authors.lastname: Lee
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Riexinger
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Ming
authors.initials: M
authors.lastname: Feng
authors.forename: Barry
authors.initials: B
authors.lastname: Koplowitz
authors.forename: Claudio
authors.initials: C
authors.lastname: Mapelli
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Cooper
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Christine
authors.initials: C
authors.lastname: Huang
authors.forename: William R
authors.initials: WR
authors.lastname: Ewing
authors.forename: John
authors.initials: J
authors.lastname: Krupinski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D019151:Peptide Library; D010455:Peptides; D018027:Receptors, Glucagon