Characterization of bioactive cell penetrating peptides from human cytochrome c: protein mimicry and the development of a novel apoptogenic agent.

Cell penetrating peptides (CPPs) with intrinsic biological activities offer a novel strategy for the modulation of intracellular events. QSAR analysis identified CPPs within human cytochrome c. Two such sequences, Cyt c(77-101) and Cyt c(86-101), induced tumor cell apoptosis, thus mimicking the role...

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Main Authors: Jones, S, Holm, T, Mäger, I, Langel, U, Howl, J
Format: Journal article
Language:English
Published: 2010
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author Jones, S
Holm, T
Mäger, I
Langel, U
Howl, J
author_facet Jones, S
Holm, T
Mäger, I
Langel, U
Howl, J
author_sort Jones, S
collection OXFORD
description Cell penetrating peptides (CPPs) with intrinsic biological activities offer a novel strategy for the modulation of intracellular events. QSAR analysis identified CPPs within human cytochrome c. Two such sequences, Cyt c(77-101) and Cyt c(86-101), induced tumor cell apoptosis, thus mimicking the role of Cyt c as a key regulator of programmed cell death. Quantitative analyses confirmed that Cyt c(77-101) is an extremely efficient CPP. Thus, Cyt c(77-101) was selected for modification to incorporate target-specific peptidyl motifs. Chimeric N-terminal extension with a target mimetic of FG nucleoporins significantly enhanced the apoptogenic potency of Cyt c(77-101) to a concentration readily achievable in vivo. Moreover, this construct, Nup153-Cyt c, facilitates the dramatic redistribution of nuclear pore complex proteins and thus propounds the nuclear pore complex as a novel target for the therapeutic induction of apoptosis.
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spelling oxford-uuid:9ccd1f05-b15a-4b97-ae8a-1b12289294772022-03-27T00:38:46ZCharacterization of bioactive cell penetrating peptides from human cytochrome c: protein mimicry and the development of a novel apoptogenic agent.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9ccd1f05-b15a-4b97-ae8a-1b1228929477EnglishSymplectic Elements at Oxford2010Jones, SHolm, TMäger, ILangel, UHowl, JCell penetrating peptides (CPPs) with intrinsic biological activities offer a novel strategy for the modulation of intracellular events. QSAR analysis identified CPPs within human cytochrome c. Two such sequences, Cyt c(77-101) and Cyt c(86-101), induced tumor cell apoptosis, thus mimicking the role of Cyt c as a key regulator of programmed cell death. Quantitative analyses confirmed that Cyt c(77-101) is an extremely efficient CPP. Thus, Cyt c(77-101) was selected for modification to incorporate target-specific peptidyl motifs. Chimeric N-terminal extension with a target mimetic of FG nucleoporins significantly enhanced the apoptogenic potency of Cyt c(77-101) to a concentration readily achievable in vivo. Moreover, this construct, Nup153-Cyt c, facilitates the dramatic redistribution of nuclear pore complex proteins and thus propounds the nuclear pore complex as a novel target for the therapeutic induction of apoptosis.
spellingShingle Jones, S
Holm, T
Mäger, I
Langel, U
Howl, J
Characterization of bioactive cell penetrating peptides from human cytochrome c: protein mimicry and the development of a novel apoptogenic agent.
title Characterization of bioactive cell penetrating peptides from human cytochrome c: protein mimicry and the development of a novel apoptogenic agent.
title_full Characterization of bioactive cell penetrating peptides from human cytochrome c: protein mimicry and the development of a novel apoptogenic agent.
title_fullStr Characterization of bioactive cell penetrating peptides from human cytochrome c: protein mimicry and the development of a novel apoptogenic agent.
title_full_unstemmed Characterization of bioactive cell penetrating peptides from human cytochrome c: protein mimicry and the development of a novel apoptogenic agent.
title_short Characterization of bioactive cell penetrating peptides from human cytochrome c: protein mimicry and the development of a novel apoptogenic agent.
title_sort characterization of bioactive cell penetrating peptides from human cytochrome c protein mimicry and the development of a novel apoptogenic agent
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