Cholecystokinin analogues with high affinity and selectivity for brain membrane receptors

VICTOR J. HRUBY, SUNAN FANG, RICHARD KNAPP, WIESLAW KAZMIERSKI, GEORGE K. LUI, HENRY I. YAMAMURA

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

A series of CCK analogues in which positions 28 and 31 have been replaced by N‐methylnorleucine residues have been synthesized. It has been found that most of these N‐methylnorleucine containing analogues of CCK are highly potent and some are extraordinarily selective for the central vs. peripheral receptor in two animal models (guinea pig and rat). [N‐MeNle28.31] CCK26–333 nonsulfated exhibited both high potency (IC50= 0.13 nM) and selectivity for central vs. peripheral receptors. The pancrease to brain cortex binding affinity ratio for this analogue IS 5100 in the rat model. NMR studies reveal that there is cis/trans isomerism about the N‐methylnorleucine residue that may be related to high selectivity.

Original languageEnglish (US)
Pages (from-to)566-573
Number of pages8
JournalInternational journal of peptide and protein research
Volume35
Issue number6
DOIs
StatePublished - Jun 1990

Keywords

  • CCK B receptors
  • CCK analogues
  • NMR analysis
  • receptor selectivity
  • receptors

ASJC Scopus subject areas

  • Biochemistry

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