Document Detail


Stopped-flow studies on drug-protein binding. Analog-computer analysis of the pH-dependent binding kinetics of warfarin and human serum albumin.
MedLine Citation:
PMID:  7121617     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Binding curves obtained by the stopped-flow method for the association of warfarin and human serum albumin (HSA) at pH 6.0 and 9.0 have been analysed with digital- and analog computers. The first association product (WHSA') at pH 6-9 does not contribute to the observed fluorescence enhancement during warfarin-HSA complex formation. A similar consecutive relaxation process leads to a more stable warfarin-HSA complex, with HSA in the neutral (N)-form (pH 6) and base (B)-form (pH 9). This rearrangement can be measured by stopped-flow (k 2 = 31 s-1 at pH 6; K'2 = 63 s-1 at pH 9). At pH 6 a further concentration dependent relaxation process has been observed indicating that the complex of warfarin with the N-form of HSA gets partially converted into its B-form with a half-time for this N leads to B transition in the range of 0.2-0.4 s. A drug such as warfarin can act as effector molecule for conformational changes of the HSA tertiary and quaternary structure during the formation of a high affinity complex.
Authors:
A Lassmann; N Rietbrock
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  320     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  1982 Aug 
Date Detail:
Created Date:  1982-12-02     Completed Date:  1982-12-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  189-95     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Computers, Analog
Humans
Hydrogen-Ion Concentration
Kinetics
Pharmaceutical Preparations / metabolism*
Protein Binding
Serum Albumin / metabolism
Spectrometry, Fluorescence
Warfarin / blood*
Chemical
Reg. No./Substance:
0/Pharmaceutical Preparations; 0/Serum Albumin; 81-81-2/Warfarin

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


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