Solution conformational preferences of a peptidic analogue of a natural macrolide(436 views) D'Andrea LD, Mazzeo M, Isernia C, Rossi F, Saviano M, Gallo P, Paolillo L, Pedone C
Keywords: Conformation, Cyclic Peptides, Fk506, Fk506 Binding Proteins, Molecular Dynamics, Chemical Bonds, Nuclear Magnetic Resonance Spectroscopy, Sulfur Compounds, Synthesis (chemical), Water, Natural Microlide, Polypeptides, Cyclopeptide, Macrolide, Article, Drug Conformation, Drug Structure, Drug Synthesis, Structure Analysis,
Affiliations: CSB CNR, Dipartimento di Chimica, USN 'Federico II', via Mezzocannone 4, 80134 Napoli, Italy
References: Not available.
Solution conformational preferences of a peptidic analogue of a natural macrolide
The conformational behavior in solution of a cyclic peptide with sequence cyclo-(Pro-1-Pro-2-Dab-3 (cHexA)psi(N-gamma-HCO)-Leu-4-psi(NHCO)-Suc-5-Gly-6-) has been thoroughly 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 a cis-cis and the second by a trans-cis Gly-Pro-Pro configuration; the trans-cis isomer was fully characterized.
Solution conformational preferences of a peptidic analogue of a natural macrolide