title: Design, synthesis, and binding affinities of pyrrolinone-based somatostatin mimetics.
abstract: [structure: see text] Tetrapyrrolinone somatostatin (SRIF) mimetics (cf. 1), based on a heterochiral (D,L-mixed) pyrrolinone scaffold, were designed, synthesized, and evaluated for biological activity. The iterative synthetic sequence, incorporating the requisite functionalized coded and noncoded amino acid side chains, comprised a longest linear synthetic sequence of 23 steps. Binding affinities at two somatostatin receptor subtypes (hsst 4 and 5) reveal micromolar activity, demonstrating that the d,l-mixed pyrrolinone scaffold can be employed to generate functional mimetics of peptide beta-turns.
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
authors.forename: Adam K
authors.initials: AK
authors.lastname: Charnley
authors.forename: Eugen F
authors.initials: EF
authors.lastname: Mesaros
authors.forename: Osamu
authors.initials: O
authors.lastname: Kikuchi
authors.forename: Wenyong
authors.initials: W
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Benowitz
authors.forename: Chi-Lien
authors.initials: CL
authors.lastname: Chu
authors.forename: Jin-Jye
authors.initials: JJ
authors.lastname: Feng
authors.forename: Kuo-Hsin
authors.initials: KH
authors.lastname: Chen
authors.forename: Atsui
authors.initials: A
authors.lastname: Lin
authors.forename: Fong-Chi
authors.initials: FC
authors.lastname: Cheng
authors.forename: Laurie
authors.initials: L
authors.lastname: Taylor
authors.forename: Ralph
authors.initials: R
authors.lastname: Hirschmann
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D015195:Drug Design; D006727:Hormone Antagonists / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D011487:Protein Conformation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D006727:Hormone Antagonists; D007202:Indicators and Reagents; D008024:Ligands; D011758:Pyrroles; D017481:Receptors, Somatostatin; D013004:Somatostatin