Achieving cell penetration with distance-matching cysteine cross-linkers: a facile route to cell-permeable peptide dual inhibitors of Mdm2/Mdmx

We report the design of bisarylmethylene bromides as a new class of rigid, distance-matching cysteine cross-linkers. By cross-linking a peptide dual inhibitor of Mdm2/Mdmx containing cysteines at i,i+7 positions, dramatic enhancement in cell permeability was achieved, along with increased helicity a...

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Published inChemical communications (Cambridge, England) Vol. 47; no. 33; pp. 9396 - 9398
Main Authors Muppidi, Avinash, Wang, Zhiyong, Li, Xiaolong, Chen, Jiandong, Lin, Qing
Format Journal Article
LanguageEnglish
Published CAMBRIDGE Royal Soc Chemistry 07.09.2011
Subjects
Amino Acid Sequence
Cell Membrane Permeability
Chemistry
Chemistry, Multidisciplinary
Cysteine - chemistry
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
HeLa Cells
Humans
Microscopy, Confocal
Nuclear Proteins - antagonists & inhibitors
Nuclear Proteins - metabolism
Peptides - chemistry
Peptides - pharmacology
Physical Sciences
Proto-Oncogene Proteins - antagonists & inhibitors
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors
Proto-Oncogene Proteins c-mdm2 - metabolism
Science & Technology
APOPTOSIS
BH3 HELIX
DESIGN
ACTIVATION
PROTEIN
RING-CLOSING METATHESIS
HELICAL PEPTIDES
STABILIZATION
MDM2
P53
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Summary:We report the design of bisarylmethylene bromides as a new class of rigid, distance-matching cysteine cross-linkers. By cross-linking a peptide dual inhibitor of Mdm2/Mdmx containing cysteines at i,i+7 positions, dramatic enhancement in cell permeability was achieved, along with increased helicity and biological activity.
Bibliography:NIH RePORTER
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1359-7345
1364-548X
DOI:10.1039/c1cc13320a