Opioid infidelity: Novel opioid peptides with dual high affinity for delta- and mu-receptors

被引:33
作者
Lazarus, LH
Bryant, SD
Salvadori, S
Attila, M
Jones, LS
机构
[1] UNIV FERRARA, DEPT PHARMACEUT SCI, I-44100 FERRARA, ITALY
[2] HELSINKI UNIV, DEPT PHARM, SF-00014 HELSINKI, FINLAND
[3] UNIV S CAROLINA, DEPT ANAT & DEV BIOL, COLUMBIA, SC 29208 USA
关键词
D O I
10.1016/0166-2236(96)81864-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Deltorphins represent the paragon of delta-opioid-receptor ligands of natural origin, since they exceed the affinity and selectivity of the endogenous enkephalins by orders of magnitude. A series of opioid peptides have been developed in which the change in a single amino acid causes an extraordinary increase in mu-receptor binding while maintaining high affinity for the delta-receptor. The peptides appear to have a similar extended conformation in solution with a type-1 p-turn in the N-terminus region, suggesting that tertiary architecture plays a pivotal role in enabling the peptide to bind indiscriminately to mu- and delta-receptors. These dual-affinity peptide ligands can serve to mask delta- and mu-receptors while mapping kappa-receptors in the nervous system, to provide an understanding of the differences and similarities in the structure of the binding domains of delta- and mu-receptors, and might lead to a comprehensive new regime for the clinical management of acute and chronic pain.
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收藏
页码:31 / 35
页数:5
相关论文
共 63 条
[1]  
ABDELHAMID EE, 1991, J PHARMACOL EXP THER, V258, P299
[2]  
AMODEO P, 1992, PEPTIDE RES, V5, P48
[3]  
ARAKAWA K, 1993, TRANSPLANT P, V25, P738
[4]  
ATTILA M, 1993, INT J PEPT PROT RES, V42, P550
[5]   INTRATHECAL DERMORPHINE IN POSTOPERATIVE ANALGESIA [J].
BASSO, N ;
MARCELLI, M ;
GINALDI, A ;
DEMARCO, M .
PEPTIDES, 1985, 6 :177-179
[6]   TOPOGRAPHICAL CONFORMATIONS OF THE DELTORPHINS PREDICATE DELTA-OPIOID RECEPTOR AFFINITY [J].
BRYANT, SD ;
SALVADORI, S ;
ATTILA, M ;
LAZARUS, LH .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (18) :8503-8504
[7]  
BRYANT SD, 1994, PEPTIDE RES, V7, P175
[8]  
DERRICK BE, 1992, J PHARMACOL EXP THER, V263, P725
[9]   THE OPIOID-PEPTIDES OF THE AMPHIBIAN SKIN [J].
ERSPAMER, V .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 1992, 10 (01) :3-30
[10]   CLONING OF A DELTA OPIOID RECEPTOR BY FUNCTIONAL EXPRESSION [J].
EVANS, CJ ;
KEITH, DE ;
MORRISON, H ;
MAGENDZO, K ;
EDWARDS, RH .
SCIENCE, 1992, 258 (5090) :1952-1955