Undesired versus designed enzymatic cleavage of linkers for liver targeting.
Bioorg Med Chem Lett
; 24(4): 1144-7, 2014 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-24461291
ABSTRACT
A design for the selective release of drug molecules in the liver was tested, involving the attachment of a representative active agent by an ester linkage to various 2-substituted 5-aminovaleric acid carbamates. The anticipated pathway of carboxylesterase-1-mediated carbamate cleavage followed by lactamization and drug release was frustrated by unexpectedly high sensitivity of the ester linkage toward hydrolysis by carboxylesterase-2 and other microsomal components.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbamates
/
Carboxylic Ester Hydrolases
/
Drug Design
/
Amino Acids, Neutral
/
Carboxylesterase
/
Liver
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2014
Document type:
Article
Affiliation country:
Estados Unidos