Conformational analysis of potent and very selective δ opioid dipeptide antagonists
1995; Wiley; Volume: 377; Issue: 3 Linguagem: Inglês
10.1016/0014-5793(95)01374-1
ISSN1873-3468
AutoresPietro Amodeo, Gianfranco Balboni, Orlando Crescenzi, Remo Guerrini, Delia Picone, Severo Salvadori, Teodorico Tancredi, P. A. Temussi,
Tópico(s)Pharmacological Receptor Mechanisms and Effects
ResumoThe δ selectivity and antagonism of peptides containing l ‐tetrahydro‐3‐isoquinoline carboxylic acid (Tic) in second position can be attributed mainly to the Tyr‐Tic unit. These properties can be further enhanced by substituting Tyr 1 with 2,6‐dimethyl‐ l ‐tyrosyl (Dmt). Dmt‐Tic‐NH 2 , Dmt‐Tic‐OH, Dmt‐Tic‐Ala‐NH 2 and Dmt‐Tic‐Ala‐OH are all more active and/or selective than the corresponding [Tyr 1 ]‐parent peptides. In fact the selectivities of Dmt‐Tic‐OH and Dmt‐Tic‐Ala‐OH are the highest ever recorded for opioid molecules. 1 H NMR spectra in a DMSO/water mixture at 278 K reveal the presence of two similar conformers, characterised by a cis or trans Dmt‐Tic bond, in all four peptides. A detailed conformational analysis in solution of Dmt‐Tic‐NH 2 shows that these conformers have a shape very similar to that of the bioactive conformation of Tyr‐Tic‐NH 2 and to that of naltrindole.
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