Part of the Advances in Experimental Medicine and Biology book series (volume 611)
Conformation-activity relationships of cyclo-constrained μ/5 opioid agonists derived from the N-terminal tetrapeptide segment of dermorphin/deltorphin
The N-terminal tetrapeptide segments of dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH 2) and deltorphin (Tyr-D-Ala-Phe-Asp/Glu-Val-Val-Gly-NH 2) are agonists at the opioid receptors μ and δ, respectively. (D-Arg 2,Lys 4)-dermorphin(1–4) amide (Tyr-D-Arg-Phe-Lys-NH 2, DALDA) and [Dmt 1]DALDA (Dmt is 2′,6′-dimethyl-tyrosine) are among the most potent and selective μ-agonists reported to date, both in vitro (the latter one having picomolar μ receptor affinity) and in vivo. In this communication, conformation-activity studies of cyclic tetrapeptide analogs of dermorphin/deltorphin are presented and discussed. They include the peptide Tyr-c[D-Cys-Phe-Cys]NH 2, constrained via an S yS ′y disulfide between Cys 2 and Cys 4, and its dicarba analogs, the C yC ′y-saturated and -olefinic ones. They are potent nonselective or moderately μ-selective opioid agonists in vitro [ 1] (Table 1). With a major structural constraint imposed by the 11-membered ring spanning residues 2–4, they are expected to...
KeywordsOpioid Agonist Proton Chemical Shift Agonist Potency Spectrum TOCSY Flexible Peptide
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This work was funded by Polish Ministry of Science and Higher Education (grants BW/8000-5-0376-7, BW/8000-5-0058-7) and by grants from the CIHR and NIH.
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