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Solution conformational preferences of a peptidic analogue of a natural macrolide
Author(s) -
D'Andrea Luca D.,
Mazzeo Marco,
Isernia Carla,
Rossi Filomena,
Saviano Michele,
Gallo Pasquale,
Paolillo Livio,
Pedone Carlo
Publication year - 1997
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/(sici)1097-0282(199709)42:3<349::aid-bip7>3.0.co;2-m
Subject(s) - chemistry , cyclic peptide , molecular dynamics , peptide , stereochemistry , sequence (biology) , molecular conformation , elongation , nuclear magnetic resonance spectroscopy , conformational change , molecule , computational chemistry , biochemistry , organic chemistry , materials science , metallurgy , ultimate tensile strength
The conformational behavior in solution of a cyclic peptide with sequence cyclo‐(Pro 1 ‐Pro 2 ‐Dab 3 (cHexA)ψ[N 7 HCO]‐Leu 4 ψ[NHCO]‐Suc 5 ‐Gly 6 ‐) has been throughly investigated with the combined use of nmr and molecular dynamic techniques. The compound, which has been modeled to mimic the FK506 macrolide bound to the FK506 binding protein structure, can be considered as a peptidic analogue of the FK506 system. The synthesis was carried out on a phenylacetoamidomethyl resin using an appropriate protocol for the peptide chain elongation. The conformational properties of the cyclic hexapeptide were studied in DMSO and water. The nmr data in DMSO and restrained molecular dynamics simulations show the presence of two contiguous cis peptide bonds involving the ‐Gly‐Pro‐Pro‐ segment. This segment in water exhibits conformational heterogeneity presenting at least two distinct conformational families, characterized the first by cis‐cis and the second by a trans‐cis Gly‐Pro‐Pro configuration; the trans‐cis isomer was fully characterized. © 1997 John Wiley & Sons, Inc. Biopoly 42: 349–361, 1997