CONFORMATIONAL-ANALYSIS OF CYCLO(2,9)-AC-QCRSVEGSCG-OH FROM THE C-TERMINAL LOOP OF HUMAN GROWTH-HORMONE

A 10 amino acid residue cyclic peptide, ln1-Cys2-Arg3-Ser4-Val5-Glu6-G ly7-Ser8-Cys9-Gly10, from the C-terminal region of human growth hormon e (hGH) was synthesized and studied by 2D proton NMR and molecular dyn amics (MD) simulations. The solubility of the peptide was low in water ; hence, NMR studies were done in two solvent mixtures, water and deut erated dimethyl sulfoxide. NOE-constrained molecular dynamics and MD s imulations resulted in major and minor conformers in solution. The maj or conformer has a type I beta-turn at Gln1-Cys2-Arg3-Ser4 and a loop structure around Glu6-Gly7-Ser8. Comparison of the conformation of thi s peptide with the peptide fragment 181-190 in the intact hGH protein X-ray crystal structure indicated that the synthetic peptide retains s ome structural similarity to the intact protein. Since the C-terminal region is important in binding the hGH protein to its receptor, the co nformation of the synthetic peptide could be useful in understanding t he binding mechanism. (C) Munksgaard 1997.