Document Detail


Role of surface exposed tryptophan as substrate generators in the antibody catalyzed water oxidation pathway.
MedLine Citation:
PMID:  23136850     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The reduction of singlet oxygen to hydrogen peroxide via the antibody catalyzed water oxidation pathway (ACWOP) has been reported (Nieva and Wentworth, Trends in Biochem. Sci, 2004, 29, 274-278). While conserved and buried tryptophans in the antibody are thought to play a major role in this pathway, our studies with a monoclonal antibody, mAb-1 and its mutant W53A, clearly demonstrate the role of surface-exposed tryptophans in substrate generation for ACWOP. Reactive oxygen species (ROS) such as singlet oxygen and superoxide were detected and site-specific tryptophan (Trp53) oxidation was observed under these conditions using RP-HPLC and mass spectrometry. The single mutant of the surface exposed Trp53 to Ala53 (W53A) results in a 50% reduction in hydrogen peroxide generated under these conditions indicating that surface exposed tryptophans contribute significantly to ROS generated via this pathway. ACWOP potentially leads to the chemical instability of mAb-1 via the generation of ROS and is important to consider during clinical and pharmaceutical development of mAbs.
Authors:
Alavattam Sreedhara; Kimberly Lau; Charlene Li; Brian Hosken; Frank Macchi; Dejin Zhan; Amy Shen; Daniel Steinmann; Christian Schoneich; Yvonne Lentz
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-9
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  -     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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