Natural peptide analgesics: the role of solution conformation |
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Authors: | R Spadaccini PA Temussi |
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Institution: | (1) Dipartimento di Chimica, Università di Napoli Federico II, Via Cinthia, 80126 Naples (Italy), Fax +39 081 674090, e-mail: pat@chemistry.unina.it , IT |
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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 proved very difficult.
First, structural studies of peptides in general are hampered by their intrinsic flexibility. Second, the relationship between
constitution and the so-called 'bioactive conformation' is far from obvious. Ideally, a direct structural study of the complex
between a peptide and its receptor should answer both questions, but such a study is not possible, because opioid receptors
are large membrane proteins, difficult to study by standard structural techniques. Thus, conformational studies of opioid
peptides are still important for drug design and also for indirect receptor mapping. This review deals with conformational
studies of natural opioid peptides in several solvents that mimic in part the different environments in which the peptides
exert their action. None of the structural investigations yields a convincing bioactive conformation, but the global conformation
of longer peptides in biomimetic environments can shed light on the interaction with receptors.
Received 15 April 2001; received after revision 10 May 2001; accepted 11 May 2001 |
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Keywords: | , Opioid, peptide, NMR, biomimetic environment, osmolyte, conformation, |
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