Document Detail


Highly specific substrates of proteinase 3 containing 3-(2-benzoxazol-5-yl)-l-alanine and their application for detection of this enzyme in human serum.
MedLine Citation:
PMID:  20361767     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A set of benzoxazolyl-l-alanine derivates along with the MCA moiety (donors of fluorescence) were introduced into a proteinase 3 (PR3) substrate with a C-terminal ANB-NH(2) that serves as a fluorescence acceptor. Five substrates with general formula X-Tyr-Tyr-Abu-ANB-NH(2) were synthesized, and their kinetic parameters against proteinase 3 were determined. The highest k(cat)/K(M) value, 1.5 x 10(6) M(-1) s(-1), was obtained for (Pyr)Box-Ala-Tyr-Tyr-Abu-NH(2) where (Pyr)Box-Ala stands for N-methylpyrrole benzoxazole-l-alanine. Titration of this peptide with proteinase 3 resulted in measurable fluorescence at an enzyme amount equal to 29 pmol. This substrate was selected used to detect quantifiable levels of proteinase 3 in serum samples, including those of normal subjects. For all c-ANCA-positive samples (diagnosed Wegener granulomatosis), a significant increase of PR3 concentration was observed. Wegener granulomatosis is a severe autoimmune disease causing inflammation of the blood vessels. Our results clearly show that this substrate can be used for the construction of a very reliable, inexpensive, and easy to use diagnostic test for PR3 determination.
Authors:
Magdalena Wysocka; Adam Lesner; Katarzyna Guzow; Julia Kulczycka; Anna Łegowska; Wiesław Wiczk; Krzysztof Rolka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Analytical chemistry     Volume:  82     ISSN:  1520-6882     ISO Abbreviation:  Anal. Chem.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-30     Completed Date:  2010-08-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370536     Medline TA:  Anal Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3883-9     Citation Subset:  IM    
Affiliation:
Faculty of Chemistry, University of Gdanìsk, Poland.
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MeSH Terms
Descriptor/Qualifier:
Alanine / chemistry*
Benzoxazoles / chemistry*
Blood Chemical Analysis / methods*
Diagnostic Techniques and Procedures / economics,  standards
Humans
Molecular Structure
Myeloblastin / blood*
Reproducibility of Results
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Substrate Specificity
Chemical
Reg. No./Substance:
0/Benzoxazoles; 56-41-7/Alanine; EC 3.4.21.76/Myeloblastin

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


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