Nuclear magnetic resonance analyses of side chain conformations of histidine and aromatic amino acid derivatives. Solvent and pH dependence.
Stereoselectively beta-deuterated species were synthesized of Ac-His-NHMe, Ac-His-OEt, Ac-His-OH and H-His-NHMe, which are useful as models of histidine residues in peptides. From the spectral comparison of 1H n.m.r., the beta-proton resonances of the normal species were unambiguously assigned. In (C2H3)2SO, C2(2)H5O2H, C2H3O2H, and C5(2)H5N solution and in aqueous solution, the lower-field and higher-field components of beta-proton resonances of the four histidine derivatives are assigned to the pro-R and pro-S protons, respectively. The alternative assignments apply for Ac-His-NHMe, Ac-His-OEt and Ac-His-OH in non-polar solvents such as C2HCl3. Vicinal coupling constants 3J alpha beta S and 3J alpha beta R were obtained for calculating the fractional populations of rotamers about the C alpha-C beta bond. The rotamer populations depend little on the ionization states of the alpha-amino and carboxyl groups or the imidazole ring. The rotamer populations depend significantly on the solvent polarity, similar to those of Phe, Tyr and Trp derivatives. For the two beta-proton resonances of His, Phe, Tyr, and Trp derivatives in a variety of solvents, linear relationships are found between the differences in chemical shifts and the differences in vicinal coupling constants.
D006639:Histidine / Q000031:analogs & derivatives*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010649:Phenylalanine / Q000031:analogs & derivatives; D011487:Protein Conformation; D012997:Solvents; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives; D014443:Tyrosine / Q000031:analogs & derivatives
D007202:Indicators and Reagents; D012997:Solvents; D014443:Tyrosine; D010649:Phenylalanine; D006639:Histidine; D014364:Tryptophan