Revisiting the structure of a synthetic somatostatin analogue for peptide drug design.

Fili, Stavroula; Valmas, Alexandros; Spiliopoulou, Maria; Kontou, Paraskevi; Fitch, Andrew; Beckers, Detlef; Degen, Thomas; Barlos, Kleomenis; Barlos, Kostas K.; Karavassili, Fotini; Margiolaki, Irene

Natural or artificially manufactured peptides attract scientific interest worldwide owing to their wide array of pharmaceutical and biological activities. X‐ray structural studies are used to provide a precise extraction of information, which can be used to enable a better understanding of the function and physicochemical characteristics of peptides. Although it is vulnerable to disassociation, one of the most vital human peptide hormones, somatostatin, plays a regulatory role in the endocrine system as well as in the release of numerous secondary hormones. This study reports the successful crystallization and complete structural model of octreotide, a stable octapeptide analogue of somatostatin. Common obstacles in crystallographic studies arising from the intrinsic difficulties of obtaining a suitable single‐crystal specimen were efficiently overcome as polycrystalline material was employed for synchrotron and laboratory X‐ray powder diffraction (XPD) measurements. Data collection and preliminary analysis led to the identification of unit‐cell symmetry [orthorhombic, P212121, a = 18.5453 (15), b = 30.1766 (25), c = 39.798 (4) Å], a process which was later followed by complete structure characterization and refinement, underlying the efficacy of the suggested (XPD) approach.

DRUG design; PEPTIDE drugs; PEPTIDE hormones; X-ray powder diffraction; ENDOCRINE system; SOMATOSTATIN; BENZENESULFONAMIDES; PEPTIDE antibiotics

Acta Crystallographica Section B: Structural Science, Crystal Engineering & Materials, 2019, Vol 75, Issue 4, p611

2052-5192

Academic Journal

10.1107/S2052520619006012