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Conformational investigations on analogs of inflammation response inducing chemotactic tripeptide fMLP
Author(s) -
Rathore Ravindranath Singh
Publication year - 2005
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20231
Subject(s) - chemistry , intramolecular force , antiparallel (mathematics) , hydrogen bond , stereochemistry , tripeptide , peptide , crystal structure , dipeptide , molecule , crystallography , cyclic peptide , isostere , turn (biochemistry) , biochemistry , physics , organic chemistry , quantum mechanics , magnetic field
Conformations of three analogs of for– L ‐Met– L ‐Leu– L ‐Phe–OH (fMLP), which initiates inflammatory response by interaction with the formyl peptide receptor (FPR), have been investigated by the application of the X‐ray crystallographic technique. The investigated analogs of fMLP peptides are as follows: for– L ‐Met‐1–amino‐1–cyclooctane–carbonyl(Ac 8 c)– L ‐Phe–OMe ( 1 ); for– L ‐Met– L ‐Leu– L ‐p‐ iodo‐Phe–OH ( 2 ); and for– L ‐Met–di‐n‐propylglycyl(Dpg)– L ‐Phe–OMe ( 3 ). The peptide backbone in 1 and 3 is constrained at position 2 of fMLP by the introduction of C α,α ‐disubstituted glycines. In peptide 2 , Phe–OMe is substituted by p‐iodo‐Phe–OH. Crystal structures reveal an overall folded conformation adopted by 1 and 2 . The former is folded in the type II β‐turn, which is stabilized by an intramolecular 1 ← 4 (formyl) CO · · · HN (Phe) hydrogen bond, whereas the latter is folded in an open turn without any intramolecular hydrogen bond. On the other hand, peptide 3 has an extended conformation, and two different molecules ( 3a, 3b ) in a crystallographic asymmetric unit form an antiparallel β‐sheet‐like structure. In 1 and 3 , residues Ac 8 c and Dpg adopt left‐handed helical and fully extended (C 5 ) conformations, respectively. The cyclooctane ring in Ac 8 c acquires a boat‐chair conformation. Crystal packing of 1 is characterized by the association of aliphatic‐aromatic rings via a CH · · · π interaction. In the crystal of 2 , contrary to the usual observations, peptides are interlinked via networks of head‐to‐tail hydrogen bond and π · · · π interactions, which are generally observed to be mutually exclusive. The structure–function mechanism of the ligand–receptor interaction is discussed. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 80: 651–664, 2005 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com