Undesired versus designed enzymatic cleavage of linkers for liver targeting.
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ABSTRACT:
SUBMITTER: Chirapu SR
PROVIDER: S-EPMC4319531 | biostudies-literature | 2014 Feb
REPOSITORIES: biostudies-literature
Publications
Undesired versus designed enzymatic cleavage of linkers for liver targeting.
Chirapu Srinivas R SR Bauman Jonathan N JN Eng Heather H Goosen Theunis C TC Strelevitz Timothy J TJ Sinha Subhash C SC Dow Robert L RL Finn M G MG
Bioorganic & medicinal chemistry letters 20140108 4
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. ...[more]
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