title: Helices with additional H-bonds: crystallographic conformations of α,γ-hybrid peptides helices composed of β-hydroxy γ-amino acids (statines).
abstract: β-Hydroxy-γ-amino acids (Statines) are a class of naturally occurring non-ribosomal amino acids frequently found in many peptide natural products. Peptidomimetics constituted with statines have been used as inhibitors for various aspartic acid proteases. In contrast to the synthetic γ-amino acids, very little is known about the folding behavior of these naturally occurring β-hydroxy γ-amino acids. To understand the folding behavior of statines, three α,γ-hybrid peptides P1 (Ac-Aib-γPhe-Aib-(R, S)Phesta-Aib-γPhe-Aib-CONH2), P2 (Ac-Aib-γPhe-Aib-(S, S)Phesta-Aib-γPhe-Aib-CONH2), and P3 (Ac-Aib-γPhe-Aib-(S, S)Phesta-Aib-(S, S)Phesta-Aib-CONH2) were synthesized on solid phase and their helical conformations in single crystals were studied. Results suggest that both syn and anti diastereoisomers of statines can be accommodated into the helix without deviating overall helical conformation of α,γ-hybrid peptides. In comparison with syn diastereoisomer, the anti diastereoisomer was found to be directly involved in the intramolecular H-bonding with the backbone carbonyl groups (i to i + 3) similar to the backbone amide NHs in the helix.
authors: Department of Chemistry, Indian Institute of Science Education and Research-Pune, Dr. Homi Bhabha Road, Pune, 411008, India.
authors: Ankita
authors: A
authors: Malik
authors: Department of Chemistry, Indian Institute of Science Education and Research-Pune, Dr. Homi Bhabha Road, Pune, 411008, India.
authors: Mothukuri Ganesh
authors: MG
authors: Kumar
authors: Department of Chemistry, Indian Institute of Science Education and Research-Pune, Dr. Homi Bhabha Road, Pune, 411008, India.
authors: Anupam
authors: A
authors: Bandyopadhyay
authors: Department of Chemistry, Indian Institute of Science Education and Research-Pune, Dr. Homi Bhabha Road, Pune, 411008, India.
authors: Hosahudya N
authors: HN
authors: Gopi
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D000596:Amino Acids; D010455:Peptides; C013165:statine
keywords: H-bonds; X-ray; amino acids; conformations; peptides