Effective Inhibition of Cellular ROS Production by MXCXXC-Type Peptides: Potential Therapeutic Applications in Copper-Homeostasis Disorders

Michal S. Shoshan; Edit Y. Tshuva

doi:10.1002/chem.201601017

Effective Inhibition of Cellular ROS Production by MXCXXC-Type Peptides: Potential Therapeutic Applications in Copper-Homeostasis Disorders

Michal S. Shoshan
, Edit Y. Tshuva^*

^*Corresponding author for this work

Institute of Chemistry

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Cyclic and acyclic peptides with sequences derived from metallochaperone binding sites, but differing at position 2, were analyzed for their inhibitory reactivity towards cellular ROS (reactive oxygen species) formation and catalytic activity towards oxidation with H₂O₂, in comparison with three commercial drugs clinically employed in chelation therapy for Wilson's disease. Acyclic peptides were more effective inhibitors than the cyclic ones, with one leading peptide with threonine at position 2 systematically showing the highest efficiency in reducing cellular ROS levels and in inhibiting Cu oxidation. This peptide was more effective than all commercial drugs in all aspects analyzed, and showed no toxicity towards human colon HT-29 cancer cells at concentrations 10–100 times higher than the IC₅₀of the commercial drugs, corroborating its high medicinal potential.

Original language	English
Pages (from-to)	9077-9081
Number of pages	5
Journal	Chemistry - A European Journal
Volume	22
Issue number	27
DOIs	https://doi.org/10.1002/chem.201601017
State	Published - 27 Jun 2016

Bibliographical note

Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ROS
Wilson's disease⋅
copper
metallochaperones
peptides

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10.1002/chem.201601017

Cite this

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title = "Effective Inhibition of Cellular ROS Production by MXCXXC-Type Peptides: Potential Therapeutic Applications in Copper-Homeostasis Disorders",

abstract = "Cyclic and acyclic peptides with sequences derived from metallochaperone binding sites, but differing at position 2, were analyzed for their inhibitory reactivity towards cellular ROS (reactive oxygen species) formation and catalytic activity towards oxidation with H2O2, in comparison with three commercial drugs clinically employed in chelation therapy for Wilson's disease. Acyclic peptides were more effective inhibitors than the cyclic ones, with one leading peptide with threonine at position 2 systematically showing the highest efficiency in reducing cellular ROS levels and in inhibiting Cu oxidation. This peptide was more effective than all commercial drugs in all aspects analyzed, and showed no toxicity towards human colon HT-29 cancer cells at concentrations 10–100 times higher than the IC50of the commercial drugs, corroborating its high medicinal potential.",

keywords = "ROS, Wilson's disease⋅, copper, metallochaperones, peptides",

author = "Shoshan, \{Michal S.\} and Tshuva, \{Edit Y.\}",

note = "Publisher Copyright: {\textcopyright} 2016 WILEY-VCH Verlag GmbH \& Co. KGaA, Weinheim",

year = "2016",

month = jun,

day = "27",

doi = "10.1002/chem.201601017",

language = "אנגלית",

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T1 - Effective Inhibition of Cellular ROS Production by MXCXXC-Type Peptides

T2 - Potential Therapeutic Applications in Copper-Homeostasis Disorders

AU - Shoshan, Michal S.

AU - Tshuva, Edit Y.

PY - 2016/6/27

Y1 - 2016/6/27

N2 - Cyclic and acyclic peptides with sequences derived from metallochaperone binding sites, but differing at position 2, were analyzed for their inhibitory reactivity towards cellular ROS (reactive oxygen species) formation and catalytic activity towards oxidation with H2O2, in comparison with three commercial drugs clinically employed in chelation therapy for Wilson's disease. Acyclic peptides were more effective inhibitors than the cyclic ones, with one leading peptide with threonine at position 2 systematically showing the highest efficiency in reducing cellular ROS levels and in inhibiting Cu oxidation. This peptide was more effective than all commercial drugs in all aspects analyzed, and showed no toxicity towards human colon HT-29 cancer cells at concentrations 10–100 times higher than the IC50of the commercial drugs, corroborating its high medicinal potential.

AB - Cyclic and acyclic peptides with sequences derived from metallochaperone binding sites, but differing at position 2, were analyzed for their inhibitory reactivity towards cellular ROS (reactive oxygen species) formation and catalytic activity towards oxidation with H2O2, in comparison with three commercial drugs clinically employed in chelation therapy for Wilson's disease. Acyclic peptides were more effective inhibitors than the cyclic ones, with one leading peptide with threonine at position 2 systematically showing the highest efficiency in reducing cellular ROS levels and in inhibiting Cu oxidation. This peptide was more effective than all commercial drugs in all aspects analyzed, and showed no toxicity towards human colon HT-29 cancer cells at concentrations 10–100 times higher than the IC50of the commercial drugs, corroborating its high medicinal potential.

KW - ROS

KW - Wilson's disease⋅

KW - copper

KW - metallochaperones

KW - peptides

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JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 27

ER -

Effective Inhibition of Cellular ROS Production by MXCXXC-Type Peptides: Potential Therapeutic Applications in Copper-Homeostasis Disorders

Abstract

Bibliographical note

UN SDGs

Keywords

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