A proton magnetic resonance study of the conformation of methionine-enkephalin as a function of pH

Abstract

It is found that methionine-enkephalin has at least two different conformations in aqueous solution, one at low and one at high pH. From inspection of titration curves and coupling constant values, it seems reasonable to conclude that these conformations are characterized by a folding so as to bring the two ends of the molecule in close proximity. This behavior parallels that found recently in (CD3)2SO as the solvent. It follows that the Phe-Met region of the molecule constitutes a relatively rigid region, but that the chain possesses flexibility around the first Gly residue. Possible implications of this behavior with respect to the receptor site are discussed.

270‐MHz 1H Nuclear‐Magnetic‐Resonance Study of Met‐enkephalin in Water

“…The resemblance observed between the cationic and zwitterionic conformational states of the backbone suggests that the conclusions drawn at acid pH can be extrapolated to the zwitterionic form. The temperature coefficients obtained at temperatures between 0°C and 75"C, reported in Table 5, are in agreement with those found by Bleich [7] and are all higher than the corresponding coefficients reported for Met-enkephalin in (C'H3)zSO [14,15]. They are within the characteristic range of solvated peptides ( A 6 NHjA T > 13 x ppm/K) and indicate that the amide protons of the -Gly-Gly-Phe-Met fragment are exposed to the solvent and free of intramolecular hydrogen bonds.…”

Averaging of φ2 and φ3 in [5‐leucyl]‐enkephalin

“…Tabulations of chemical shifts and coupling constants from these figures are in table 1. At pH 7, in agreement with the observations in water/DMSO solution [2], the Hl resonance is broadened beyond detection, and HJ resonances are buried by the Phe4 H' signal.…”

Conformational flexibility in enkephalins: Solvent dependent transitions in peptides with Gly‐Gly segments detected by circular dichroism

“…The widespread interest in developing structureactivity correlations for opioid peptides [1][2][3] has led to a large number of investigations on the preferred solution conformations of enkephalins [4][5][6][7][8][9][10][11]. The results of these studies have led to proposals ranging from/3-turn conformations.…”

“…The results of these studies have led to proposals ranging from/3-turn conformations. With Gly2-Gly 3 [14] or Gly3-Phe 4 [4][5][6][7][8][9][10] as the corner residues. Evidence for the lack of preferred conformations in solutions, resulting from dynamic averaging between an ensemble of structures, has also been presented [ 11 ].…”