title: Conformational analysis of two somatostatin analogues by 1H 500 MHz n.m.r. spectroscopy.
abstract: A series of nine closely related somatostatin analogues, containing the hexapeptide H-Cys2-Phe3-D-Trp4-Lys5-Thr6-Cys7-NH2 sequence have been synthesized by Bauer et al. The conformational properties of two of them, showing intermediate activities between those of SMS 201-995 and somatostatin, have been studied by high field n.m.r. spectroscopy in DMSO. Assignments were made using 2D-n.m.r. methods, in particular NOESY experiments and detection of long-range connectivities in aromatic residues. In all the compounds of this series, the biologically active ones as well as the inactive ones, the n.m.r. parameters are in favour of a predominant conformation with a type II' beta turn involving amino acids Phe3 to Thr6. A clearcut correlation exists between the predominant conformation at the cystine bridge side and the activity. The presence of the exocyclic amino acids Phe1 and Thr8 (ol) plays a major role in stabilization of the active conformation.
mesh_terms: D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011487:Protein Conformation; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D013004:Somatostatin