Informed Development of Drugs Acting at Family B G Protein-Coupled Receptors

被引：3

作者：

Miller, Laurence J. ^{[1
]}

机构：

[1] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ 85259 USA

来源：

Neural Signaling: Opportunities for Novel Diagnostic Approaches and Therapies | 2008年 / 1144卷

基金：

美国国家卫生研究院;

关键词：

G protein-coupled receptors; receptor structure; ligand binding; activation mechanisms; secretin receptor;

D O I：

10.1196/annals.1418.001

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Rational refinement and development of receptor-active ligands can come from high-resolution insights into the structures of these potential drug targets. Structural insights for Family A G protein-coupled receptors (GPCRs) have been advanced substantially with the recently reported crystal structure of the intact beta 2-adrenergic receptor. While high-resolution structural insights for Family B GPCRs are also advancing, this is currently limited to the functionally important extracellular amino-terminal tail domain of those receptors. The current report describes how these structures can provide leads for the development of small-molecule agonist drugs acting at Family B GPCRs. Endogenous agonist activity within the amino terminus of these receptors could be key for the development of such drugs.

引用

页码：203 / 209

页数：7

共 29 条

[1] Structural insights into the amino-terminus of the secretin receptor: I. Status of cysteine and cystine residues [J].

Asmann, YW ;

Dong, MQ ;

Ganguli, S ;

Hadac, EM ;

Miller, LJ .

MOLECULAR PHARMACOLOGY, 2000, 58 (05) :911-919

[2] Parathyroid hormone-receptor interactions identified directly by photocross-linking and molecular modeling studies [J].

Bisello, A ;

Adams, AE ;

Mierke, DF ;

Pellegrini, M ;

Rosenblatt, M ;

Suva, LJ ;

Chorev, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (35) :22498-22505

[3] High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor [J].

Cherezov, Vadim ;

Rosenbaum, Daniel M. ;

Hanson, Michael A. ;

Rasmussen, Soren G. F. ;

Thian, Foon Sun ;

Kobilka, Tong Sun ;

Choi, Hee-Jung ;

Kuhn, Peter ;

Weis, William I. ;

Kobilka, Brian K. ;

Stevens, Raymond C. .

SCIENCE, 2007, 318 (5854) :1258-1265

[4] Molecular approximations between residues 21 and 23 of secretin and its receptor: Development of a model for peptide docking with the amino terminus of the secretin receptor [J].

Dong, Maoqing ;

Lam, Polo C. -H. ;

Gao, Fan ;

Hosohata, Keiko ;

Pinon, Delia I. ;

Sexton, Patrick M. ;

Abagyan, Ruben ;

Miller, Laurence J. .

MOLECULAR PHARMACOLOGY, 2007, 72 (02) :280-290

[5] Possible endogenous agonist mechanism for the activation of secretin family G protein-coupled receptors [J].

Dong, Maoqing ;

Pinon, Delia I. ;

Asmann, Yan W. ;

Miller, Laurence J. .

MOLECULAR PHARMACOLOGY, 2006, 70 (01) :206-213

[6] Identification of two pairs of spatially approximated residues within the carboxyl terminus of secretin and its receptor [J].

Dong, MQ ;

Asmann, YW ;

Zang, MW ;

Pinon, DI ;

Miller, LJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (34) :26032-26039

[7] Spatial approximation between the amino terminus of a peptide agonist and the top of the sixth transmembrane segment of the secretin receptor [J].

Dong, MQ ;

Li, ZJ ;

Pinon, DI ;

Lybrand, TP ;

Miller, LJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (04) :2894-2903

[8] Spatial approximation between two residues in the mid-region of secretin and the amino terminus of its receptor - Incorporation of seven sets of such constraints into a three-dimensional model of the agonist-bound secretin receptor [J].

Dong, MQ ;

Li, ZJ ;

Zang, MQ ;

Pinon, DI ;

Lybrand, TP ;

Miller, LJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (48) :48300-48312

[9] Identification of an interaction between residue 6 of the natural peptide ligand and a distinct residue within the amino-terminal tail of the secretin receptor [J].

Dong, MQ ;

Wang, Y ;

Hadac, EM ;

Pinon, DI ;

Holicky, E ;

Miller, LJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (27) :19161-19167

[10] Interaction among four residues distributed through the secretin pharmacophore and a focused region of the secretin receptor amino terminus [J].

Dong, MQ ;

Zang, MW ;

Pinon, DI ;

Li, ZJ ;

Lybrand, TP ;

Miller, LJ .

MOLECULAR ENDOCRINOLOGY, 2002, 16 (11) :2490-2501

← 1 2 3 →