Document Detail


The High-affinity Maltose Switch MBP317-347 has Low Affinity for Glucose: Implications for Targeting Tumors with Metabolically-Directed Enzyme Prodrug Therapy.
MedLine Citation:
PMID:  24131788     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Development of agents with high affinity and specificity for tumor-specific markers is an important goal of molecular-targeted therapy. Here, we propose a shift in paradigm using a strategy that relies on low affinity for fundamental metabolites found in different concentrations in cancerous and non-cancerous tissues: glucose and lactate. A molecular switch, MBP317-347, originally designed to be a high-affinity switch for maltose and maltose-like polysaccharides, was demonstrated to be a low-affinity switch for glucose, i.e. able to be activated by high concentrations (tens of millimolar) of glucose. We propose that such a low-affinity glucose switch could be used as a proof of concept for a new prodrug therapy strategy denominated Metabolically-Directed Enzyme Prodrug Therapy (MDEPT) where glucose or, preferably, lactate serves as the activator. Accordingly, considering the typical differential concentrations of lactate found in tumors and in healthy tissues, a low-affinity lactate-binding switch analogous to the low-affinity glucose-binding switch MBP317-347 would be an order of magnitude more active in tumors than in normal tissues and, therefore, can work as a differential activator of anticancer drugs in tumors. This article is protected by copyright. All rights reserved.
Authors:
Gilmer Valdes; Reinhard W Schulte; Marc Ostermeier; Keisuke S Iwamoto
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Publication Detail:
Type:  LETTER     Date:  2013-10-16
Journal Detail:
Title:  Chemical biology & drug design     Volume:  -     ISSN:  1747-0285     ISO Abbreviation:  Chem Biol Drug Des     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-10-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101262549     Medline TA:  Chem Biol Drug Des     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
Affiliation:
Department of Radiation Oncology, David Geffen School of Medicine at UCLA.
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