Structure and conformation of peptides containing the sulfonamide junction. II. Synthesis and conformation of cyclo[-MeTau-Phe-DPro-].
By applying the method of amino-acyl incorporation to sulfonamido peptides, cyclo(-MeTau-Phe-DPro-) 3 has been synthesized in high yield starting from Z-MeTau-Phe-Pro-OH. The crystal structure and the molecular conformation of 3 have been determined. Crystals are orthorhombic, s.g. P2(1)2(1)2(1), with a = 5.454, b = 13.486, c = 24.025 A. The structure has been solved by direct methods and refined to R = 0.039 for 1974 reflections with I greater than 1.5 sigma (I). The 10-measured cyclopeptide adopts a backbone conformation in the crystals characterized by Phe-DPro and DPro-MeTau peptide bonds in trans and cis conformation, respectively. Both the peptide bonds deviate significantly from planarity and the corresponding [delta omega[ values are ca. 12 degrees. The sulfonamide SO2NH junction adopts a cisoidal conformation with a C alpha 1-S1-N2-C alpha 2 torsion angle of 70.8 degrees. 13C n.m.r. data show that the trans geometry at the Phe-DPro junction found in the crystals is retained in DMSO solution. The 10-membered ring of 3 is characterized by a pseudo mirror-plane passing through the Phe nitrogen and the DPro carbonylic carbon. The DPro ring adopts a half-chair conformation. The Phe side chain conformation corresponds to the statistically most favored g- rotamer (chi 1 = -68.6 degrees). The crystal packing is characterized by a weak intermolecular hydrogen bond between NH group and the MeTau O1' oxygen.
Calcagni
A
A
Department of Pharmaceutical Studies, University, La Sapienza, Rome, Italy.
Gavuzzo
E
E
Lucente
G
G
Mazza
F
F
Pinnen
F
F
Pochetti
G
G
Rossi
D
D
D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D005583:Fourier Analysis; D006859:Hydrogen; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis; D010456:Peptides, Cyclic; D011487:Protein Conformation; D014961:X-Ray Diffraction
D009842:Oligopeptides; D010456:Peptides, Cyclic; C063946:cyclo(methyltauryl-phenylalanyl-proline); D006859:Hydrogen