Nuclear-magnetic-resonance study of aggregations and conformations of melanostatin and related peptides.
The 1H and 13C nuclear magnetic resonance spectra of melanostatin (Pro-Leu-Gly-NH2) and related peptides (Pro-Leu-Gly, Z-Pro-Leu-Gly, Z-Pro-Leu-Gly-NH2 and Z-Pro-Leu-Gly-OCH3, where Z = benzyloxycarbonyl) were analysed in a variety of solvents. At physiological pH, the melanostatin molecule is N-protonated in aqueous solution. The concentration dependences of the chemical shifts of amide-proton and carbonyl-carbon resonances and of proton spin-lattice relaxation times were observed in relation to molecular aggregations. In dimethylsulfoxide solution, aggregations were observed for N-protonated melanostatin and Pro-Leu-Gly prepared with HCl and for the Na salt of Z-Pro-Leu-Gly but not for N-protonated melanostatin prepared with HClO4 or HNO3, unprotonated melanostatin, Z-Pro-Leu-Gly-NH2, or Z-Pro-Leu-Gly-OCH3. The leucine NH and glycine CO groups of N-protonated melanostatin are involved in the intermolecular hydrogen bonds of aggregates. The leucine NH group of N-protonated Pro-Leu-Gly also forms the intermolecular hydrogen bond. The solvent and temperature dependences of the chemical shifts of amide-proton and carbonyl-carbon resonances were measured to determine intramolecular hydrogen bonding. In dimethylsulfoxide solution, N-protonated melanostatin molecules in part take the beta-turn structure and the trans carboxamide NH proton and carbonyl oxygen of the proline residue form an intramolecular hydrogen bond.
D005998:Glycine; D007930:Leucine; D009075:MSH Release-Inhibiting Hormone; D009682:Magnetic Resonance Spectroscopy; D011392:Proline; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D009075:MSH Release-Inhibiting Hormone; D011392:Proline; D007930:Leucine; D005998:Glycine