Eicosapentaenoic acid and prevention of atherosclerosis.
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Arteriosclerosis↗
Biomedical subjects
P Amodeo
Publications and source records attributed to P Amodeo.
Delta-selective opioid peptides containing a single aromatic residue in the message domain: an NMR conformational analysis.
The sequence of deltorphin I, a delta-selective opioid agonist, has been systematically modified by inserting conformationally constrained C alpha, alpha disubstituted apolar residues in the third position. As expected, substitution of Phe with Ac6c, Ac5c and Ac3c yields analogues with decreasing but sizeable affinity. Surprisingly, substitution with Aib yields an analogue with almost the same binding affinity of the parent compound but with a greatly increased selectivity. This is the first case of a potent and very selective opioid peptide containing a single aromatic residue in the message domain, that is, only Tyr1. Here we report a detailed conformational analysis of [Aib3]deltorphin I and [Ac6c3]deltorphin I in DMSO at room temperature and in a DMSO/water cryomixture at low temperature, based on NMR spectroscopy and energy calculations. The peptides are highly structured in both solvents, as indicated by the exceptional finding of a nearly zero temperature coefficient of Val5 NH resonance. NMR data cannot be explained on the basis of a single structure but it was possible to interpret all NMR data on the basis of a few structural families. The conformational averaging was analysed by means of an original computer program that yields qualitative and quantitative composition of the mixture. Comparison of the preferred solution conformation with two rigid delta-selective agonists shows that the shapes of [Aib3]deltorphin I and [Ac6c3]deltorphin I are consistent with those of rigid agonists and that the message domain of opioid peptides can be defined only in conformational terms.
Animals↗
Solution structure of deltorphin I at 265 K: a quantitative NMR study.
Deltorphin I, a delta-selective opioid peptide, has been studied in a DMSOd6/H2O cryoprotective mixture by two-dimensional (2D) NMR spectroscopy in the temperature range 260 K to 305 K. The high viscosity of the solvent at low temperature mimics a distinctive physico-chemical feature of cytoplasm and allows the measurement of a NOESY spectrum rich in intra- and inter-residue effects. Backbone NOEs at 265 K can be calculated with good accuracy in terms of only two limiting conformers: one folded, with a mole fraction of 0.30, and another extended with a mole fraction of 0.70. This calculation is still a rough approximation of the complex conformational equilibria existing in solution but, to the best of our knowledge, is the first one for a flexible peptide, and represents an encouraging starting point for a quantitative evaluation of NMR data of small, flexible peptides in solution. The folded conformer consistent with observed NOEs has a shape surprisingly similar to those of unrelated, rigid, delta-selective opiates.
Amino Acid Sequence↗