The micelle-associated 3D structures of Boc-Y(SO3)-Nle-G-W-Nle- D-2-phenylethylester (JMV-180) and CCK-8(s) share conformational elements of a calculated CCK1 receptor-bound model

Mohanraja Kumar, Joseph R. Reeve, Weidong Hu, Laurence J. Miller, David A. Keire

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

JMV-180 (1) and CCK-8(s) are high affinity ligands at the CCK1 receptor that have similar and different actions via this receptor. Here we calculate the tertiary structure of 1 or CCK-8(s) in the presence of dodecylphosphocholine micelles at pH 5.0 and 35°C from 2D 1H NMR data recorded at 600 MHz. The NMR derived 3D structures of 1 and CCK-8(s) share a common type I β-turn around residues Nle3/M3 and G4 and diverge from each other structurally at the N- and C-termini. The fluorescence and circular dichroism spectral properties of these peptides are consistent with their NMR derived structures. The structures determined in the presence of DPC micelles are compared to available models of 1 or CCK-8(s) bound to the CCK1 receptor. For CCK and 1, these comparisons show that DPC micelle associated structures duplicate some important aspects of the models calculated from cross-linking derived constraints at the CCK1 receptor.

Original languageEnglish (US)
Pages (from-to)3742-3754
Number of pages13
JournalJournal of Medicinal Chemistry
Volume51
Issue number13
DOIs
StatePublished - Jul 10 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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