| Abstract: | The conformations of a pentapeptide L -His-L -Arg-L -Trp-Gly with weak adrenocorticotropin (ACTH) activity and its analogs, where each L -amino acid residue is substituted by D -residue, were investigated by means of proton and carbon-13 nmr spectroscopy on their DMSO-d6 solutions. The spectra indicated the presence of slowly exchangeable conformation isomers for D -Phe and D -Arg analogs, due to steric hindrance around the arginine residue. The activation energy of the hindered rotation of the arginine side chain was estimated to be more than 19 ～ 20 kcal/mol. Spin-lattice relaxation times of carbon-13 nuclei also indicated slow segmental motion of the arginine side chain of the D analogs. An effect on proton chemical shifts by intermolecular electrostatic interaction between the arginine side chain and the C terminal carboxylic residue was observed. We did not observe, however, a direct correlation between pentapeptide activity and molecular conformation at this stage of the experiments. |
