The structure and conformation of the tryptophanyl diketopiperazines cyclo(Trp-Trp) centre dot C_2H_6SO anc cyclo(Trp-Pro)

摘要

The structure and conformation of the cyclic dipeptides [cyclo(L-Trp-L-Trp) centre dot C_2H_6SO] and cyclo(L-Trp-L-Pro) have been investigated with X-ray crystallographic and spectroscopic methods. Cyclo(L-tryptophanyl-L-tryptophanyl) centre dot DMSO solvate crystallized in the space group P2_12_12_1 with cell dimensions a = 6.193(2), b = 11.545(3), c = 31.117(4) A. The crystal structure is stabilized by four hydrogen bonds (three intermolecular hydrogen bonds and one intramolecular bond). The first intermolecular bond is between the oxygen of DMSO and the nitrogen of indole ring 2, in contrast to the second intramolecular hydrogen bond between the nitrogen of indole ring 1 and the oxygen of DMSO. The two remaining intermolecular hydrogen bonds are between 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 extended side chain conformation for Trp residue 1 (E_N) and a folded conformation for Trp residue 2. The DKP ring is more planar than in other cyclic dipeptide compounds (#phi#_1 = 11.414, #psi#_1 = -7.516, #phi#_2 = 12.471, and #phi#_2 = -8.256). In cyclo(L-Trp-L-Trp) the C#beta# resonance of L-tryptophan (29.88 ppm) is shifted upfield 0.82 ppm when compared with the same resonance in cyclo(L-Trp-L-Gly) (30.7 ppm) and cyclo(L-Leu-L-Trp) (30.7 ppm). Two conformations 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) A, #alpha# = 80.42(1), #beta# = 78.61(1), and #gamma# = 89.13(1) deg. The conformation of the backbone and the orientation of the aromatic side chains for these conformers are very similar. The DKP rings for both conformers adopt a typical boat conformation in contrast to the flattened chair conformation observed for cyclo(Tyr-Pro) and cyclo(Phe-F-Pro). The tryptophan side chains of these conformers are folded towards the diketopiperazine (DKP) ring. The pyrrolidine ring for conformer 1 can be described as an envelope (Cs-C#beta#-endo) conformation in contrast to the pyrrolidine ring symmetry for conformer 2 which is an intermediate between C_s and C_2 rather than pure C_s for the proline ring with C#beta#-endo and C#gamma#-exo with respect to C'. The two prolyl rings are puckered at the #beta#-carbon atoms which deviate form the best planes defined by the four remaining atoms. The crystal structures are stabilized by four intermolecular hydrogens bonds. An intermolecular bond between 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 between 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 oxygens 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 DKP ring (conformer 1)------carbonyl oxygen of DKP ring (conformer 2)].