CONFORMATIONAL-ANALYSIS OF HUMAN GROWTH-HORMONE-[6-13] PEPTIDE ANALOGS

The conformational analysis of a series of ten hGH[6-13] peptide analo gues is reported. As part of our earlier studies, the alpha-aminosucci nimide modified fragment Asu(11)-hGH[6-13] has previously been identif ied as a potentiator of insulin activity in intravenous insulin tolera nce tests, and various analogues have been subsequently designed, synt hesised and employed to acquire structure-activity data. These studies have lead to the conclusion that the conformational characteristics a t the C-terminus of each of the active peptide analogues is important to the biological activity. In the present investigation, molecular dy namics and simulated annealing techniques have been used to examine th e accessible conformational states of the C-terminal region of ten dif ferent hGH[6-13] peptide analogues. Of these six are active peptide an alogues while the other four show no biological activity. Examination of the conformer groups identified using this molecular dynamics appro ach showed a common conformational motif for each of the active peptid es. (C) Munksgaard 1996.