Inferences about the conformation of somatostatin at a biologic receptor based on NMR studies

Examination of two diastereomeric analogs of somatostatin differing in stereochemistry at the tryptophan residue has revealed a high field resonance in the -Trp isomer which is assigned to the γ-methylene of Lys⁹. The extent of correlation of this shift with biologic activity for a series of analogs of somatostatin is discussed. From comparison of close analogs, it is suggested that the biologically active conformation of somatostatin at the receptor controlling insulin release is not the major conformation of this hormone in solution. It is suggested that the conformation of somatostatin at this receptor resembles more closely the solution conformation of analogs having tryptophan in the -configuration. This latter conformation places the Trp⁸-Lys⁹ side chains in close proximity, thus shifting the γ-methylene protons of Lys⁹ upfield.