Predicting the physicochemical profile of diastereoisomeric histidine-containing dipeptides by property space analysis.

Détails

ID Serval
serval:BIB_DEA543E8ED1B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Predicting the physicochemical profile of diastereoisomeric histidine-containing dipeptides by property space analysis.
Périodique
Chirality
Auteur(s)
Vistoli G., Straniero V., Pedretti A., Fumagalli L., Bolchi C., Pallavicini M., Valoti E., Testa B.
ISSN
1520-636X (Electronic)
ISSN-L
0899-0042
Statut éditorial
Publié
Date de publication
2012
Volume
24
Numéro
7
Pages
566-576
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
OBJECTIVES: This study aimed at measuring the lipophilicity and ionization constants of diastereoisomeric dipeptides, interpreting them in terms of conformational behavior, and developing statistical models to predict them.
METHODS: A series of 20 dipeptides of general structure NH(2) -L-X-(L or D)-His-OMe was designed and synthetized. Their experimental ionization constants (pK(1) , pK(2) and pK(3) ) and lipophilicity parameters (log P(N) and log D(7.4) ) were measured by potentiometry. Molecular modeling in three media (vacuum, water, and chloroform) was used to explore and sample their conformational space, and for each stored conformer to calculate their radius of gyration, virtual log P (preferably written as log P(MLP) , meaning obtained by the molecular lipophilicity potential (MLP) method) and polar surface area (PSA). Means and ranges were calculated for these properties, as was their sensitivity (i.e., the ratio between property range and number of rotatable bonds).
RESULTS: Marked differences between diastereoisomers were seen in their experimental ionization constants and lipophilicity parameters. These differences are explained by molecular flexibility, configuration-dependent differences in intramolecular interactions, and accessibility of functional groups. Multiple linear equations correlated experimental lipophilicity parameters and ionization constants with PSA range and other calculated parameters.
CONCLUSION: This study documents the differences in lipophilicity and ionization constants between diastereoisomeric dipeptides. Such configuration-dependent differences are shown to depend markedly on differences in conformational behavior and to be amenable to multiple linear regression. Chirality 24:566-576, 2012. © 2012 Wiley Periodicals, Inc.
Pubmed
Web of science
Création de la notice
22/07/2012 22:00
Dernière modification de la notice
03/03/2018 22:02
Données d'usage