Abstract
A non-internalizing αvβ3 integrin ligand was conjugated to the anticancer drug MMAE through a β-glucuronidase-responsive linker. In the presence of β-glucuronidase, only the conjugate bearing a PEG4 spacer inhibited the proliferation of integrin-expressing cancer cells at low nanomolar concentrations, indicating important structural requirements for the efficacy of these therapeutics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Glioblastoma / drug therapy*
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Glioblastoma / metabolism
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Glioblastoma / pathology
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Glucuronidase
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Humans
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Integrin alphaVbeta3 / antagonists & inhibitors*
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Integrin alphaVbeta3 / chemistry
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Integrin alphaVbeta3 / metabolism
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Ligands
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Molecular Conformation
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Structure-Activity Relationship
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Vitronectin / antagonists & inhibitors
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Vitronectin / chemistry
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Vitronectin / metabolism
Substances
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Antineoplastic Agents
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Integrin alphaVbeta3
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Ligands
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Oligopeptides
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Vitronectin
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Glucuronidase
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monomethyl auristatin E