Impact of ß-perfluoroalkyl substitution of proline on the proteolytic stability of its peptide derivatives.
Org Biomol Chem
; 20(47): 9337-9350, 2022 12 07.
Article
en En
| MEDLINE
| ID: mdl-36107003
ABSTRACT
A series of all stereoisomers of ß-CF3 or ß-C2F5 substituted prolines and their dipeptide derivatives were synthesized. Mouse plasma stability assay was carried out to study the impact of fluoroalkyl substituents on the proteolytic stability of proline-derived peptides. The effect of the (R)-/(S)-configuration at the C-2 atom in combination with electronic and steric effects imposed by fluoroalkyl groups was addressed to rationalize the difference in the half-life stability of diastereomeric ß-CF3-Pro-Gly and ß-C2F5-Pro-Gly derivatives and compared to those of parent (S)-Pro-Gly and (R)-Pro-Gly dipeptides. The steric effect was predominant when the ß-CF3 or ß-C2F5 group was placed properly to create a spatial interference within the pockets of proteases, thereby protecting the substances from degradation (e.g., for cis-isomeric derivatives). Otherwise, a smaller electronic effect accelerating proteolysis was in charge (i.e., for the (2S,3S) isomers).
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Prolina
/
Electrónica
Límite:
Animals
Idioma:
En
Revista:
Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Ucrania