Cholecystokinin octapeptide analogues stable to brain proteolysis

Martha Knight, Paolo Barone, Carol A. Tamminga, Luca Steardo, Thomas N. Chase

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Based on recent findings identifying the initial degradative cleavage of CCK-8 at the Met3-Gly4 bond by a metalloendopeptidase, two analogues of CCK-8 with D-Ala and D-Trp substitutions at the Gly4 position were synthesized as stable analogues. Their stability to proteolysis by brain membranes and their binding potency at central CCK receptors were quantified. Both peptides are stable to degradation by peptidases in cortical synaptic membrane preparations. The analogues are nearly equipotent to CCK-8 in their affinities for inhibition of 1251-CCK-33 binding to guinea pig cortical membranes. L-Ala and L-Trp substituted peptides were synthesized for comparison. Both these peptides are degraded by synaptic membranes and the L-Trp substituted peptide possesses a greatly reduced affinity for central CCK receptors. Therefore, the structure of CCK due to the D conformation of Gly is more capable of interacting with brain CCK receptors. Further conformational analysis will establish whether the stabilized structure is a β-bend or a β-turn. Since these peptides are highly potent and stable to brain proteolysis they may be useful as stable CCK analogues for in vivo application.

Original languageEnglish (US)
Pages (from-to)631-634
Number of pages4
Issue number4
StatePublished - Jan 1 1985


  • CCK-8 agonist
  • Neural CCK receptors
  • Neuropeptide
  • Neuropeptide proteolysis
  • Stable analogue
  • [D-Ala] CCK-8 [D-Trp] CCK-8

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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