CONFORMATION OF T-BOC-BETA-ALA-TRP-MET-ASP-PHE-NH2 (PENTAGASTRIN) BY NMR AND PCILO METHODS

Pentagastrin (t-boc-beta-Ala-Trp-Met-Asp-Phe-NH2) is a diagnostic agen t for evaluating gastric acid secretory function. The conformation of this pentapeptide has been investigated by NMR and PCILO methods. Two conformations have been predicted by PCILO calculations. The first has an extended structure at the C-terminal and is folded about the N-ter minal, with a gamma-bend at Met. in addition, the CO and NH groups of beta-Ala are involved in intramolecular hydrogen bonding. The second c onformation is nearly fully extended, except about the beta-Ala residu e where the above mentioned intramolecular hydrogen bond again appears . The first conformation is only about 1.7 kcal/mol, lower in energy a s compared to the second one. The solution conformation as determined by NMR techniques such as 2-D-COSY, NOESY, ROESY, (3)J(NH alpha) coupl ing constants and temperature coefficients of NH resonances is predomi nantly extended. The solution conformation of the peptide in lipid bil ayers was found to be an extended one. Based on these findings, the bi ologically active conformation of pentagastrin has been deduced.