Peptide-binding G protein-coupled receptors: New opportunities for drug design

被引:57
作者
Gurrath, M [1 ]
机构
[1] Univ Dusseldorf, D-40225 Dusseldorf, Germany
关键词
D O I
10.2174/0929867013371798
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Over the last decades distinct members of the G Protein-Coupled Receptor (GPCR) family emerged as prominent drug targets within pharmaceutical research, since approximately 60 % of marketed prescription drugs act by selectively addressing representatives of that class of transmembrane signal transduction systems. It is noteworthy that the majority of GPCR-targeted drugs elicit their biological activity by selective agonism or antagonism of biogenic monoamine receptors, while the development status of peptide-binding GPCR-adressing compounds is still in its infancy, Exemplified on selected medicinal chemistry projects, this review will focus on the opportunities of therapeutic intervention into a broad spectrum of disease processes through agonizing or antagonizing the functions of peptide-binding GPCRs. In this context, a brief overview of GPCR-mediated signal transduction pathways will be given in order to emphasize the biomedical relevance of a controlled modulation of receptor function. Modern trends on lead finding and optimization strategies for peptide-binding GPCR-targeted low-molecular weight compounds will be highlighted on the basis of current research programs conducted in the areas of angiotensin II, endothelin, bradykinin, neurokinin, neuropeptide Y, LHRH, C5a antagonists, and somatostatin agonists, respectively. Special emphasis will be laid on the elaboration and utilization of structural rationales on the potential drug candidates, thus facilitating more detailed insights into the underlying molecular recognition event.
引用
收藏
页码:1605 / 1648
页数:44
相关论文
共 299 条
[1]   A novel class of orally active non-peptide bradykinin B2 receptor antagonists.: 3.: Discovering bioisosteres of the imidazo[1,2-α]pyridine moiety [J].
Abe, Y ;
Kayakiri, H ;
Satoh, S ;
Inoue, T ;
Sawada, Y ;
Inamura, N ;
Asano, M ;
Aramori, I ;
Hatori, C ;
Sawai, H ;
Oku, T ;
Tanaka, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (21) :4062-4079
[2]   A novel class of orally active non-peptide bradykinin B2 receptor antagonists.: 4.: Discovery of novel frameworks mimicking the active conformation [J].
Abe, Y ;
Kayakiri, H ;
Satoh, S ;
Inoue, T ;
Sawada, Y ;
Inamura, N ;
Asano, M ;
Aramori, I ;
Hatori, C ;
Sawai, H ;
Oku, T ;
Tanaka, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (23) :4587-4598
[3]   A novel class of orally active non-peptide bradykinin B2 receptor antagonist.: 2.: Overcoming the species difference between guinea pig and man [J].
Abe, Y ;
Kayakiri, H ;
Satoh, S ;
Inoue, T ;
Sawada, Y ;
Inamura, N ;
Asano, M ;
Hatori, C ;
Sawai, H ;
Oku, T ;
Tanaka, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (21) :4053-4061
[4]   A novel class of orally active non-peptide bradykinin B2 receptor antagonists.: 1.: Construction of the basic framework [J].
Abe, Y ;
Kayakiri, H ;
Satoh, S ;
Inoue, T ;
Sawada, Y ;
Imai, K ;
Inamura, N ;
Asano, M ;
Hatori, C ;
Katayama, A ;
Oku, T ;
Tanaka, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (04) :564-578
[5]  
ADANG AEP, 1994, RECL TRAV CHIM PAY B, V113, P63
[6]  
ALEXANDER SPH, 1999, TRENDS PHARM SCI
[7]   Effects of GR203040, an NK1 antagonist, on radiation- and cisplatin-induced tissue damage in the ferret [J].
Alfieri, AB ;
Gardner, CJ .
GENERAL PHARMACOLOGY-THE VASCULAR SYSTEM, 1998, 31 (05) :741-746
[8]   Nonpeptide antagonists for kinin receptors [J].
Altamura, R ;
Meini, S ;
Quartara, L ;
Maggi, CA .
REGULATORY PEPTIDES, 1999, 80 (1-2) :13-26
[9]  
ANDERSON S, 1994, MED CHEM RENIN ANGIO, V21, P47
[10]   RESINFERATOXIN, AN ULTRAPOTENT CAPSAICIN ANALOG, HAS ANTIEMETIC PROPERTIES IN THE FERRET [J].
ANDREWS, PLR ;
BHANDARI, P .
NEUROPHARMACOLOGY, 1993, 32 (08) :799-806