Document Detail

Species-dependent binding of tocainide analogues to albumin: Affinity chromatography and circular dichroism study.
MedLine Citation:
PMID:  24472243     Owner:  NLM     Status:  Publisher    
A series of novel tocainide analogues were characterized for their HSA and RSA binding, by using high-performance liquid affinity chromatography (HPLAC) and circular dichroism (CD). In this HPLAC study, HSA and RSA were covalently immobilized to the silica matrix of HPLC columns, with a procedure that maintained unaltered the binding properties of the proteins. The tocainide analogues were ranked for their affinity to HSA and RSA on the basis of their bound fractions measured by the two albumin-based columns. This technique was also applied to characterize the high affinity binding sites of these tocainide analogues to the protein. For this purpose displacement experiments were carried out by means of increasing concentrations in the mobile phase of competitors known to bind selectively to the main binding sites of HSA. The results obtained with the immobilized proteins were confirmed by investigating the same drug-protein systems in solution by circular dichroism. The comparison of the data collected with both methodologies highlighted the dramatic effect of small differences in the amino acidic sequences of the two proteins. In fact, despite their similar primary and secondary structures, a small difference in the amino acidic sequence leads to significant differences in their three-dimensional structure reflecting their different binding capacity and their stereoselectivity. Therefore, this study confirms how it is crucial to consider the significant differences among the animal models when performing pharmacokinetic studies. It is also clear that the knowledge of serum carrier binding parameters at an early stage of drug discovery represents a great advantage that may help to save time and efforts.
Marco Pistolozzi; Cecilia Fortugno; Carlo Franchini; Filomena Corbo; Marilena Muraglia; Myriam Roy; Guy Félix; Carlo Bertucci
Related Documents :
7144923 - Interaction of calcium with 3h-morphine binding to synaptosomes of the guinea-pig ileum.
23657293 - Protein binding by dinuclear polypyridyl ruthenium(ii) complexes and the effect of cucu...
2409923 - The interaction of platelet factor four and glycosaminoglycans.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-10
Journal Detail:
Title:  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences     Volume:  -     ISSN:  1873-376X     ISO Abbreviation:  J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101139554     Medline TA:  J Chromatogr B Analyt Technol Biomed Life Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier B.V. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Sporadic hypokalemic paralysis caused by osmotic diuresis in diabetes mellitus.
Next Document:  Approaches to enhancing the early detection of autism spectrum disorders: a systematic review of the...