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Utilization of peptide carrier system to improve intestinal absorption: targeting prolidase as a prodrug-converting enzymeThe feasibility of targeting prolidase as a peptide prodrug-converting enzyme has been examined. The enzymatic hydrolysis by prolidase of substrates for the peptide transporter L-alpha-methyldopa-pro and several dipeptide analogues without an N-terminal alpha-amino group (phenylpropionylproline, phenylacetylproline, N-benzoylproline, and N-acetylproline) was investigated. The Michaelis-Menten parameters Km and Vmax for L-alpha-methyldopa-pro are 0.09 +/- 0.02 mM and 3.98 +/- 0.25 mumol/min/mg protein, respectively. However, no hydrolysis of the dipeptide analogues without an N-terminal alpha-amino group is observed, suggesting that an N-terminal alpha-amino group is required for prolidase activity. These results demonstrate that prolidase may serve as a prodrug-converting enzyme for the dipeptide-type prodrugs, utilizing the peptide carrier for transport of prodrugs into the mucosal cells and prolidase, a cytosolic enzyme, to release the drug. However, a free alpha-amino group appears to be necessary for prolidase hydrolysis.
Document ID
20050000788
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Bai, J. P.
(College of Pharmacy, University of Minnesota Minneapolis 55455)
Hu, M.
Subramanian, P.
Mosberg, H. I.
Amidon, G. L.
Date Acquired
August 22, 2013
Publication Date
February 1, 1992
Publication Information
Publication: Journal of pharmaceutical sciences
Volume: 81
Issue: 2
ISSN: 0022-3549
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: GM 37188
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Regulatory Physiology
Non-NASA Center

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