Kumar Mohanraja, Reeve Joseph R, Hu Weidong, Miller Laurence J, Keire David A
CURE: Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
J Med Chem. 2008 Jul 10;51(13):3742-54. doi: 10.1021/jm701401j. Epub 2008 Jun 10.
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.
JMV - 180（1）和CCK - 8（s）是CCK1受体的高亲和力配体，它们通过该受体具有相似和不同的作用。在此，我们根据在600 MHz记录的二维（1）H NMR数据，计算了在pH 5.0和35摄氏度下，1或CCK - 8（s）在十二烷基磷酸胆碱胶束存在时的三级结构。从NMR得出的1和CCK - 8（s）的三维结构在Nle3/M3和G4残基周围具有共同的I型β-转角，并且在N端和C端在结构上彼此不同。这些肽的荧光和圆二色光谱特性与其NMR得出的结构一致。将在DPC胶束存在下确定的结构与1或CCK - 8（s）与CCK1受体结合的现有模型进行比较。对于CCK和1，这些比较表明，与DPC胶束相关的结构复制了从CCK1受体交联衍生的约束条件计算出的模型的一些重要方面。
