Conformational properties of ascydiacyclamide analogues with cyclic α-amino acids instead of oxazoline residues.
Bioorg Med Chem
; 25(24): 6554-6562, 2017 12 15.
Article
en En
| MEDLINE
| ID: mdl-29097029
ABSTRACT
Ascidiacyclamide [ASC, cyclo(-Ile-oxazoline-d-Val-thiazole-)2] is a cyclic octapeptide isolated from tunicates. We designed ASC analogues [cyclo(-Ile-Xxx-d-Val-thiazole-)2] in which Pro or a homologue was substituted for oxazoline [Pro]ASC (Xxx proline), [Aze]ASC (Xxx (S)-Azetidine-2-carboxylic acid), [Pip]ASC (Xxx (S)-Piperidine-2-carboxylic acid) and [ΔPro]ASC (Xxx (S)-3-pyrroline-2-carboxylic acid) to explore their potential to serve as substitutes for the oxazoline ring. The conformations of these analogues were examined using X-ray diffraction, 1H NMR and CD spectroscopy. In both the crystal and solution states, the conformations of [Pro]ASC, [Aze]ASC and [ΔPro]ASC were novel square structures having two trans imide bonds and stabilized by two intramolecular hydrogen bonds. The crystal structure of [Pip]ASC was a folded conformation with cis and trans imide bonds. Three isomers (cc, ct and tt) were present in a solution of [Pip]ASC. From crystal structures, the degree of puckering in the side chains of Pro and its homologues was estimated to be in the order Pipâ¯>â¯Proâ¯>â¯Azeâ¯>â¯ΔPro. [Pro]ASC and [Pip]ASC showed strong cytotoxicity, but [Aze]ASC and [ΔPro]ASC showed no cytotoxicity. Among the four analogues, there is consistency between the prolyl ring puckering and cytotoxicity, but not between the peptide backbone structure and cytotoxicity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxazoles
/
Péptidos Cíclicos
/
Aminoácidos Cíclicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2017
Tipo del documento:
Article