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

J Med Chem. 2008 Jul 10;51(13):3742-54. doi: 10.1021/jm701401j. Epub 2008 Jun 10.

Abstract

JMV-180 ( 1) and CCK-8(s) are high affinity ligands at the CCK 1 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 degrees C from 2D (1)H NMR data recorded at 600 MHz. The NMR derived 3D structures of 1 and CCK-8(s) share a common type I beta-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 CCK 1 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 CCK 1 receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Circular Dichroism
  • Imaging, Three-Dimensional
  • Magnetic Resonance Spectroscopy
  • Micelles*
  • Models, Molecular*
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptor, Cholecystokinin A / chemistry*
  • Receptor, Cholecystokinin A / metabolism*
  • Sincalide / analogs & derivatives
  • Sincalide / chemistry*
  • Spectrometry, Fluorescence

Substances

  • Micelles
  • Receptor, Cholecystokinin A
  • JMV 180
  • Sincalide