Document Detail

Synthesis and biodistribution of Bowman-Birk soybean protease inhibitor conjugate with amphiphilic polyester.
MedLine Citation:
PMID:  9100351     Owner:  NLM     Status:  MEDLINE    
The modification of Bowman-Birk soybean protease inhibitor (BBI) with the monoaldehyde derivative of block copolymer of ethylene oxide and propylene oxide (PE), M(r) 2,000 is described. The conjugate contains five covalently bound polymer chains per protein molecule, and retains the ability to inhibit trypsin and chymotrypsin-like proteinases. The distribution of native BBI and the BBI-PE conjugate was examined in mice. After i.v. injection of [125I]BBI and [125I]BBI-PE, both inhibitors distributed very rapidly to the liver, kidney, and lungs, and more slowly to the brain. At the same time-points (up to 24 h), radioactivity in the blood and organs of mice injected with modified inhibitor was higher than that of the native inhibitor. The blood concentration time profile following i.v. administration of two BBI preparations at a dose 3 mg/kg was reasonable well described by a two-compartment open model with first-order elimination kinetics. The total clearance of BBI-PE decreased by a factor of 8, body mean residence time increased by a factor of 5 in comparison with BBI. A physiological pharmacokinetic model was developed to describe the tissue-to-blood distribution of two inhibitors. One-compartment physiological organ model (flow limited) was used to describe of time-course profiles of BBI concentration in organs. A two-compartment physiological organ model (membrane limited) was used to predict tissue-to-blood distribution of conjugated BBI in some organs of mice (liver, lungs). The predicted concentration curves of BBI and BBI-PE in blood and organs in mice (with the exception of kidney) showed good agreement with the observed values.
N I Larionova; I P Gladysheva; O V Polekhina; L P Kurochkina; E N Gorbatova
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Applied biochemistry and biotechnology     Volume:  61     ISSN:  0273-2289     ISO Abbreviation:  Appl. Biochem. Biotechnol.     Publication Date:    1996 Oct-Nov
Date Detail:
Created Date:  1997-05-13     Completed Date:  1997-05-13     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8208561     Medline TA:  Appl Biochem Biotechnol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  139-48     Citation Subset:  IM    
Department of Chemistry, M. V. Lomonosov Moscow State University, Russia.
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MeSH Terms
Chromatography, High Pressure Liquid
Epoxy Compounds
Ethylene Oxide
Macromolecular Substances
Polyesters / pharmacology*
Surface-Active Agents / pharmacology*
Tissue Distribution
Trypsin Inhibitor, Bowman-Birk Soybean / chemical synthesis*,  pharmacokinetics
Reg. No./Substance:
0/Epoxy Compounds; 0/Macromolecular Substances; 0/Polyesters; 0/Polymers; 0/Surface-Active Agents; 0/Trypsin Inhibitor, Bowman-Birk Soybean; 75-21-8/Ethylene Oxide; 75-56-9/propylene oxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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