N-ACETYL-L-PROLYL-L-LEUCYL-GLYCINAMIDE - X-RAY STRUCTURE, ENERGY MINIMIZATION AND CALORIMETRIC DETERMINATIONS

A solid-state study of N-acetyl-L-prolyl-L-leucyl-glycinamide hemihydr ate (NAPLGA), C15H26N4O4 . 0.5H(2)O has been performed using single cr ystal X-ray diffraction method and calorimetric determinations of the fusion thermodynamic parameters. Conformational energy map of Ac-Pro-L eu-Gly-NH2 molecule has also been evaluated. In the crystal, the molec ular backbone is folded back between Leu and Gly residues and the conf ormation is stabilized by a 1 <-- 4 intramolecular H-bond. In this man ner a ten-membered cyclic structure with beta-turn type II conformatio n is formed. Prolyl residue is in a slightly distorted Cs-C-beta-exo f orm and Leu side-chain adopts the energetically favoured t(g(+)t) conf ormation. Crystal packing is characterized by four intermolecular hydr ogen bonds which involve all the donor groups. The crystallization wat er placed on a binary axis acts as a bridge, through two H-bonds, betw een two-fold related peptide molecules, All the hydrogen bonds assembl e in wide layers extending parallel to the ab plane of a C2 space grou p. Along the c direction, adjacent layers are separated by regions cha racterized by loose van der Waals interactions. Potential energy calcu lations have been carried out using procedures as in ECEPP (empirical conformational energy program for peptides) and AMBER programs and the most favoured conformations have been analysed in comparison with the one observed in the hydrated crystal. The observed conformation is ve ry close to a relative minimum, whose energy is only 4 kJ mol(-1) (ECE PP procedure) higher than that of the calculated absolute minimum. The rmodynamic properties concerning the fusion, when compared with those of other correlated N-acetyl peptidoamides, suggest that the intramole cular hydrogen bond is probably maintained also in NAPLGA molten, part ially limiting the conformational freedom of each peptide molecule. (C ) 1998 Elsevier Science B.V.