Abstract
Monomethyl auristatin E (MMAE) is conjugated with TNF-related apoptosis-inducing ligand (TRAIL) via a linker that is stable in extracellular fluid, while it is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the antimitotic mechanism of MMAE. The TRAIL-MMAE conjugate is a conceptually viable therapeutic strategy with improved in vitro antitumor activity, cell circle arrest and specific accumulation in tumor to treat TRAIL-resistant tumors.
Keywords:
antitumor agents; biomedical applications; drug delivery; protein modifications; protein-protein interactions.
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / toxicity
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Apoptosis / drug effects
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Cathepsins / metabolism
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Cell Cycle Checkpoints / drug effects
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Drug Carriers / chemistry*
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Humans
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MCF-7 Cells
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Microscopy, Confocal
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Oligopeptides / chemistry*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / toxicity
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TNF-Related Apoptosis-Inducing Ligand / chemistry*
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TNF-Related Apoptosis-Inducing Ligand / genetics
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TNF-Related Apoptosis-Inducing Ligand / toxicity
Substances
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Antineoplastic Agents
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Drug Carriers
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Oligopeptides
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Recombinant Proteins
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TNF-Related Apoptosis-Inducing Ligand
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Cathepsins
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monomethyl auristatin E