Improving the passive permeability of macrocyclic peptides: Balancing permeability with other physicochemical properties.
Bioorg Med Chem
; 23(2): 322-7, 2015 Jan 15.
Article
in En
| MEDLINE
| ID: mdl-25533323
ABSTRACT
A number of methods to improve the passive permeability of a set of cyclic peptides have been investigated using 6- and 7-mer macrocyclic templates. In many cases the peptides were designed by molecular dynamics calculations to evaluate the methods. The aim of this study was not only to improve passive permeability, but also to balance permeability with other physicochemical properties with the goal of understanding and applying the knowledge to develop active cyclic peptides into drug candidates. Evaluation of the methods herein suggest that increasing passive permeability often occurs at the expense of solubility and lipophilicity. Computational methods can be useful when attempting to predict and design features to balance these properties, though limitations were observed.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides, Cyclic
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2015
Type:
Article
Affiliation country:
United kingdom