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Modified chemotactic peptides: Synthesis, conformation, and biological activity of for‐Thp‐Leu‐Δ z Phe‐OMe
Author(s) -
Torrini I.,
Zecchini G. Pagani,
Paradisi M. Paglialunga,
Lucente G.,
Gavuzzo E.,
Mazza F.,
Pochetti G.,
Traniello S.,
Spisani S.,
Cerichelli G.
Publication year - 1994
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360341002
Subject(s) - chemistry , tripeptide , chemotaxis , stereochemistry , turn (biochemistry) , lysozyme , residue (chemistry) , biological activity , superoxide , peptide , enzyme , biochemistry , receptor , in vitro
For‐Thp‐Leu‐Δ z Phe‐OMe ( 2 ), an analogue of the chemotactic tripeptide For‐Met‐Leu‐Phe‐OMe, containing 4‐aminotetrahydrothiopyran‐4‐carboxylic acid (Thp) and (Z)‐2,3‐didehydrophenylalanine (Δ z Phe) as achiral, conformationally restricted mimics of Met and Phe, respectively, has been synthesized. In the crystal the new formyltripeptide adopts a type I β‐turn conformation stabilized by a weak H bond between the formylic oxygen and the Δ z Phe NH. 1 H‐nmr analysis based on NH solvent accessibility and nuclear Overhauser effect experiments suggests that the β‐turn is not preferred in CDCl 3 solution where a γ‐turn, centered at the Thp residue, prevails. The biological activity of 2 has been determined on human neutrophils and compared to that of previously studied analogues. The tripeptide 2 is practically unable to elicit superoxide anion production and lysozyme release, while slight, but not statistically significant activity was induced in chemotaxis. The role of the orientation of the aromatic ring with respect to the backbone adjacent atoms is discussed. © 1994 John Wiley & Sons, Inc.