Structure of octreotide, a somatostatin analogue

Octreotide, a synthetic somatostatin analogue, is an octapeptide with one disulfide bridge. Crystals of octreotide are orthorhombic, space group P2₁2₁2₁, a = 18.458 (5), b = 30.009 (7), c = 39.705 (27) Å, with three molecules of octapeptide, one ordered oxalate dianion and 52 water molecules in the asymmetric unit. Complete protonation of the NH₂ groups (as assumed in the refinement) would require three oxalate dianions in the asymmetric unit for charge neutrality; a chemical analysis indicated that four are present. In either case they are so disordered that they cannot be distinguished from the water molecules. The 18 951 unique reflections (R_sym = 0.026) used for structure solution and refinement were recorded with the EMBL imaging-plate scanner using synchrotron radiation. The structure was solved by Patterson interpretation, locating the three disulfide bridges, followed by tangent phase expansion and E-Fourier recycling. The anisotropic refinement against all F² data between 1.04 and 10.0 Å resolution by blocked restrained full-matrix least-squares techniques converged to a conventional R index based on F of 0.084 [I > 2a(I) and 10.0 > d > 1.04 Å] and wR2, the weighted R-index on F², of 0.246 (for all data). One peptide molecule adopts a flat β-sheet structure; the other two possess different irregular backbone conformations, but are similar to each other. All three molecules have a distorted type II′ β-turn around the D-Trp-Lys region, but exhibit different side-chain conformations. The crystal structure is stabilized by a network of inter- and intramolecular hydrogen bonds.