Abstract
Integrins moderate diverse important functions in the human body and are promising targets in cancer therapy. Hence, the selective inhibition of specific integrins is of great medicinal interest. Here, we report the optimization of a grafted lasso peptide, yielding MccJ25(RGDF), which is a highly potent and selective αvβ3 integrin inhibitor. Furthermore, its NMR structure was elucidated and employed in a molecular dynamics approach, revealing information about the integrin binding mode and selectivity profile of MccJ25(RGDF).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacteriocins / genetics
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Cell Adhesion / drug effects
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Human Umbilical Vein Endothelial Cells / drug effects
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Humans
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Integrin alphaVbeta3 / antagonists & inhibitors*
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Integrin alphaVbeta3 / chemistry
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Models, Molecular
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Molecular Dynamics Simulation
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Nuclear Magnetic Resonance, Biomolecular
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Peptides / chemistry*
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Peptides / pharmacology
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Protein Conformation
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Snake Venoms / pharmacology
Substances
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Bacteriocins
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Integrin alphaVbeta3
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Peptides
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Snake Venoms
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microcin
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Cilengitide
Associated data
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PDB/1L5G
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PDB/1Q71
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PDB/2MMT
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PDB/2MMW