Craig Giragossian

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Intermolecular interactions were determined between a synthetic peptide corresponding to the third extracellular loop and several residues from the adjoining sixth and seventh transmembrane domains of the human cholecystokinin-1 receptor, CCK(1)-R(329-357), and the synthetic agonists Ace-Trp-Lys[NH(epsilon)CONH-o-(MePh)]-Asp-MePhe-NH(2) (GI5269) and the C1(More)
The structure of the third extracellular loop of the human cholecystokinin-2 receptor, CCK2-R(352-379), and its interactions with the C-terminal octapeptide of cholecystokinin (CCK-8) have been determined by high-resolution NMR and computer simulations. In the presence of dodecylphosphocholine micelles, the structure of the receptor fragment consisted of(More)
The interaction of the C-terminal octapeptide of cholecystokinin, CCK-8, with the third extracellular loop of human cholecystokinin-A receptor, CCK(A)-R(329-357), has been probed by high-resolution NMR and extensive computer simulations. The structure of CCK(A)-R(329-357) in the presence of dodecylphosphocholine micelles consists of three alpha-helices,(More)
A comparison of the conformational characteristics of the related hormones [Nle(15)] gastrin-17 and [Tyr(9)-SO(3)] cholecystokinin-15, in membrane-mimetic solutions of dodecylphosphocholine micelles and water, was undertaken using NMR spectroscopy to investigate the possibility of a structural motif responsible for the two hormones common ability to(More)
The interaction of peptide ligands with their associated G-protein-coupled receptors has been examined by a number of different experimental approaches over the years. We have been developing an approach utilizing high-resolution NMR to determine the structural features of the peptide ligand, well-designed fragments of the receptor, and the ligand-receptor(More)
The conformational features of a conjugate of the C-terminus of human gastrin (HG[11-17]), the shortest gastrin sequence retaining biological function, with beta-cyclodextrin ([Nle(15)]-HG[11-17]-betaCD) were determined by NMR spectroscopy in an aqueous solution of dodecylphosphocholine (DPC) micelles. The peptide-betaCD conjugate displays a binding(More)
G-protein-coupled receptors (GPCRs) allow cells to respond to calcium, hormones, and neurotransmitters. Not surprisingly, they currently make up the largest family of validated drug targets. Rational drug design for molecular regulators targeting GPCRs has been limited to theoretical-based computational approaches. X-ray crystallography of intact GPCRs has(More)
Conformational features of the C-terminal carboxyamidated pentadecapeptide of CCK (S(19)HRISDRD[SO(4)]-YMGWMDF(33)-NH(2)) were determined by NMR spectroscopy in a zwitterionic membrane-mimetic solvent system, composed of DPC micelles. The C-terminal octapeptide consisted of a well-defined pseudohelix that was nearly identical to the structure previously(More)
To date high resolution structural studies of G protein coupled receptors, with the exception of rhodopsin, have not been feasible using conventional spectroscopic techniques. To overcome these difficulties, the structural features of partial or intact domains of GPCRs have been studied by nuclear magnetic resonance spectroscopy and X-ray crystallography.(More)
The conformational features of Pam-Lys(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)-Ser(6)-Pro(7)-Phe(8)-Arg(9)-OH (PKD) and Pam-Gly(-1)-Lys(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)-Ser(6)-Pro(7)-Phe(8)-Arg(9)-OH (PGKD), the Pam-Lys and Pam-Gly-Lys analogues of bradykinin, have been determined by high-resolution NMR in a zwitterionic lipoid environment.(More)