The structure and conformation of the tryptophanyl diketopiperazines cyclo(Trp-Trp)center dot C2H6SO and cyclo(Trp-Pro)

The structure and conformation of the cyclic dipeptides [cyclo(L-Trp-L-Trp) . C2H6SO] and cyclo(L-Trp-L-Pro) have been investigated with X-ray crystall ographic and spectroscopic methods. Cyclo(L-tryptophanyl-L-tryptophanyl).DM SO solvate crystallized in the space group P2(1)2(1)2(1) with cell dimensio ns a = 6.193(2), b = 11.545(3), c = 31.117(4) Angstrom. The crystal structu re is stabilized by four hydrogen bonds (three intermolecular hydrogen bond s and one intramolecular bond). The first intermolecular bond is between th e oxygen of DMSO and the nitrogen of indole ring 2, in contrast to the seco nd intramolecular hydrogen bond between the nitrogen of indole ring 1 and t he oxygen of DMSO. The two remaining intermolecular hydrogen bonds are betw een the nitrogens of the DKP ring and the carbonyl oxygens of the DKP ring. The values of chi(1)(1A) (-45.764) and chi(2)(1A) (67.437) indicate an ext ended side chain conformation for Trp residue 1 (EN) and a folded conformat ion for Trp residue 2. The DKP ring is more planar than in other cyclic dip eptide compounds (phi(1) = 11.414, Psi(1) = -7.516, phi(2) = 12.471, and Ps i(2) = -8.256). In cyclo(L-Trp-L-Trp) the C beta resonance of L-tryptophan (29.88 ppm) is shifted upheld 0.82 ppm when compared with the same resonanc e in cyclo(L-Trp-L-Gly) (30.7 ppm) and cyclo(L-Leu-L-Trp) (30.7 ppm). Two c onformations of cyclo(Trp-Pro) crystallized in the space group P1 with cell dimensions a = 5.422(1), b = 9.902(1), c = 13.443(2) Angstrom, alpha = 80. 42(1), beta = 78.61(1), and gamma = 89.13(1)degrees. The conformation of th e backbone and the orientation of the aromatic side chains for these confor mers are very similar. The DKP rings for both conformers adopt a typical bo at conformation in contrast to the flattened chair conformation observed fo r cyclo(Tyr-Pro) and cyclo(Phe-F-Pro). The tryptophan side chains of these conformers are folded towards the diketopiperazine (DKP) ring. The pyrrolid ine ring for conformer 1 can be described as an envelope (Cs-C beta-endo) c onformation in contrast to the pyrrolidine ring symmetry for conformer 2 wh ich is an intermediate between C-s and C-2 rather than pure C-s for the pro line ring with C beta-endo and C gamma exo with respect to C'. The two prol yl rings are puckered at the beta-carbon atoms which deviate from the best planes defined by the four remaining atoms. The crystal structures are stab ilized by four intermolecular hydrogens bonds. An intermolecular bond betwe en the nitrogen of the indole ring (conformer 1) and the carbonyl oxygen of the DKP ring (conformer 2) was observed. The second hydrogen bond is betwe en the nitrogen of the indole ring (conformer 2) and the carbonyl oxygen of the DKP ring (conformer 1). The last two hydrogens involve the carbonyl ox ygens of the DKP rings and the nitrogens of the DKP rings [carbonyl oxygen of DKP ring (conformer 1)-nitrogen of DKP ring (conformer 2); nitrogen of D KP ring (conformer 1)-carbonyl oxygen of DKP ring (conformer 2)].