Properties of a novel chemotactic esapeptide, an analogue of the prototypical N-formylmethionyl peptide

Cavicchioni, Giorgio; Turchetti, Marianna; Varani, Katia; Falzarano, Sofia; Spisani, Susanna

doi:10.1016/s0045-2068(03)00070-1

Cited by 6 publications

(7 citation statements)

References 22 publications

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“…The retroisomer of fMLP, i.e., CHO–Phe–Leu–Met–NH 2 and its D analogs were found to be 100 to 10,000 times less active 74. Many other formyl peptides were also examined recently, for biological activities;75–95…”

Section: Discussionmentioning

confidence: 99%

“…To probe the structural requirement, these groups were mutated with residues having different steric, charge, and hydrophobic groups, and constraints were introduced to achieve the desired conformation. A large number of analogs of fMLP have been designed and synthesized, examined for their biological activities, and quite a few have also been studied for their conformation using X‐ray crystallography and NMR techniques 2, 9–22, 52–95. Results of conformational and activity studies on these peptides are summarized in Table V.…”

Section: Discussionmentioning

confidence: 99%

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Conformational investigations on analogs of inflammation response inducing chemotactic tripeptide fMLP

Rathore

2005

Biopolymers

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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(Ac8c)-L-Phe-OMe; for-L-Met-L-Leu-L-p-iodo-Phe-OH; and for-L-Met-di-n-propylglycyl(Dpg)-L-Phe-OMe. The peptide backbone in and is constrained at position of fMLP by the introduction of Calpha,alpha-disubstituted glycines. In peptide, Phe-OMe is substituted by p-iodo-Phe-OH. Crystal structures reveal an overall folded conformation adopted by and. The former is folded in the type II beta-turn, which is stabilized by an intramolecular 1<--4 (formyl) C==O...H--N (Phe) hydrogen bond, whereas the latter is folded in an open turn without any intramolecular hydrogen bond. On the other hand, peptide has an extended conformation, and two different molecules in a crystallographic asymmetric unit form an antiparallel beta-sheet-like structure. In and, residues Ac8c and Dpg adopt left-handed helical and fully extended (C5) conformations, respectively. The cyclooctane ring in Ac8c acquires a boat-chair conformation. Crystal packing of is characterized by the association of aliphatic-aromatic rings via a C--H...pi interaction. In the crystal of, contrary to the usual observations, peptides are interlinked via networks of head-to-tail hydrogen bond and pi...pi interactions, which are generally observed to be mutually exclusive. The structure-function mechanism of the ligand-receptor interaction is discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Conformational investigations on analogs of inflammation response inducing chemotactic tripeptide fMLP

Rathore

2005

Biopolymers

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“…2 ) production Superoxide anion production was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c modified for microplate-based assays [15]. Tests were carried out in a final volume of 200 ml containing 4 Â 10 5 neutrophils, 100 nmol cytochrome c and KRPG.…”

Section: Superoxide Anion (O àmentioning

confidence: 99%

“…Neutrophil granule enzyme release was evaluated by determining the modified lysozyme activity in microplate-based assays [15]. Cells were incubated in microplate wells in the presence of each peptide at a final concentration of 10 À10 to 10 À4 M for 15 min at 37 C. The plates were then centrifuged for 5 min at 400g, and the amount of lysozyme was quantified nephelometrically by the rate of lysis of a cell wall suspension of Micrococcus lysodeikticus.…”

Section: Granule Enzyme Assaymentioning

confidence: 99%