Solution conformational preferences of a peptidic analogue of a natural macrolide

✍ Scribed by Luca D. D'Andrea; Marco Mazzeo; Carla Isernia; Filomena Rossi; Michele Saviano; Pasquale Gallo; Livio Paolillo; Carlo Pedone

• Publisher: Wiley (John Wiley & Sons)
• Year: 1997
• Tongue: English
• Weight: 158 KB
• Volume: 42
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/(sici)1097-0282(199709)42:3<349::aid-bip7>3.0.co;2-m

✦ Synopsis

The conformational behavior in solution of a cyclic peptide with sequence cyclo-(Pro 1 -Pro 2 -Dab 3 (cHexA)c[N g HCO]-Leu 4 c[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-Prosegment. 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 transcis Gly-Pro-Pro configuration; the trans-cis isomer was fully characterized.