The Influence of the Stereochemistry of Alanine Residue on the Solid State Conformation and Crystal Packing of Opioid Peptides Containing d-Ala or l-Ala in Message Domain – XRD and NMR Study

• Published in: The journal of physical chemistry. B 2011-08, Vol.115 (32), p.9910-9919
• Main Authors: Trzeciak-Karlikowska, Katarzyna, Bujacz, Anna, Ciesielski, Włodzimierz, Bujacz, Grzegorz D, Potrzebowski, Marek J
• Format: Article
• Language: English
• Subjects: Alanine; Alanine - chemistry; B: Biophysical Chemistry; Crystallography; Crystallography, X-Ray; Models, Molecular; Molecular structure; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular - methods; Opioid Peptides - chemistry; Peptides; Protein Conformation; Residues; Stereochemistry; Stereoisomerism; X-ray diffraction
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp205570y

In this work, an X-ray diffraction (XRD) and solid state NMR study of two tetrapeptides with different stereochemistry of alanine residue is presented using Tyr-(d-Ala)-Phe-Gly (1), an N-terminal sequence of opioid peptide dermorphin, and its biologically inactive analog Tyr-(l-Ala)-Phe-Gly (2). Single-crystal XRD proved that 1 crystallized under different conditions from exclusively one structure: a monoclinic crystal with P21 space group. In contrast, 2 very easily formed at least three crystallographic modifications, 2a (monoclinic P21), 2b (orthorhombic P21212) and 2c (tetragonal P41212). Solid-state NMR spectroscopy was employed to investigate the structure and molecular dynamics of 1, 2a, and 2b. By employing different NMR experiments (dipolar dephasing and PILGRIM) and an analysis of the 13C principal elements of the chemical shift tensor (CST), it was proven that the main skeleton of tetrapeptides is rigid, whereas significant differences in the molecular motion of the aromatic residues were observed. Comparing current data with those of previous studies (J. Phys. Chem. B 2004, 108, 4535–4545 and Cryst. Growth Des. 2009, 9, 4050–4059), it can be assumed that an important preorganization mechanism anticipating the formation of peptide crystals containing d-Ala in sequence is the intramolecular CH−π interaction, which occurs for the amino acid with D stereochemistry. This effect may be responsible for the formation of only one crystallographic form of d-Ala peptides.