Natural peptide analgesics: the role of solution conformation

Citation
R. Spadaccini et Pa. Temussi, Natural peptide analgesics: the role of solution conformation, CELL MOL L, 58(11), 2001, pp. 1572-1582
Citations number
100
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELLULAR AND MOLECULAR LIFE SCIENCES
ISSN journal
1420682X → ACNP
Volume
58
Issue
11
Year of publication
2001
Pages
1572 - 1582
Database
ISI
SICI code
1420-682X(200110)58:11<1572:NPATRO>2.0.ZU;2-W
Abstract
Endogenous opioids have been studied extensively since their discovery, in the hope of finding a perfect analgesic, devoid of the secondary effects of alkaloid opioids. However, the design of selective opioid agonists has pro ved very difficult. First, structural studies of peptides in general are ha mpered by their intrinsic flexibility. Second, the relationship between con stitution and the so-called 'bioactive conformation' is far from obvious. I deally, a direct structural study of the complex between a peptide and its receptor should,answer both questions, but such a study is not possible, be cause opioid receptors are large membrane proteins, difficult to study by s tandard structural techniques. Thus, conformational studies of opioid pepti des are still important for drug design and also for indirect receptor mapp ing. This review deals with conformational studies of natural opioid peptid es in several solvents that mimic in part the different environments in whi ch the peptides exert their action. None of the structural investigations y ields a convincing bioactive conformation, but the global conformation of l onger peptides in biomimetic environments can shed light on the interaction with receptors.