Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119

Philipp M. Cromm; Hélène Adihou; Shobhna Kapoor; Mercedes Vazquez-Chantada; Paul Davey; David Longmire; Elisabeth Hennes; Walter Hofer; Philipp Küchler; Elisabetta Chiarparin; Herbert Waldmann; Tom N. Grossmann

doi:10.1002/cbic.201900615

Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119

Philipp M. Cromm
, Hélène Adihou
, Shobhna Kapoor
, Mercedes Vazquez-Chantada
, Paul Davey
, David Longmire
, Elisabeth Hennes
, Walter Hofer
, Philipp Küchler
, Elisabetta Chiarparin
, Herbert Waldmann^*
, Tom N. Grossmann

^*Corresponding author for this work

AIMMS

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

The acyl-binding UNC119 proteins mediate the activation and transport of various N-myristoylated proteins. In particular, UNC119a plays a crucial role in the completion of cytokinesis. Herein, we report the use of a lipidated peptide originating from the UNC119 binding partner Gnat1 as the basis for the design of lipidated, stabilized α-helical peptides that target UNC119a. By using the hydrocarbon peptide-stapling approach, cell-permeable binders of UNC119a were generated that induced the accumulation of cytokinetic and binucleated cells; this suggests UNC119a as a potential target for the inhibition of cytokinesis.

Original language	English
Pages (from-to)	2987-2990
Number of pages	4
Journal	ChemBioChem
Volume	20
Issue number	24
Early online date	23 Nov 2019
DOIs	https://doi.org/10.1002/cbic.201900615
Publication status	Published - 13 Dec 2019

Funding

We thank Christine Nowak and Mamta Jaiswal for protein expression/purification and technical assistance. P.M.C. is grateful to the Studienstiftung des deutschen Volkes for a fellowship. T.N.G. thanks the European Research Council (ERC starting grant, no. 678623) for the support.

Funders	Funder number
European Research Council
Studienstiftung des Deutschen Volkes
Horizon 2020 Framework Programme	678623
???publication-publication-funding-organisation-not-added???	13353

Keywords

alpha-helixes
macrocyclization
peptidomimetics
protein–protein interaction
trafficking

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10.1002/cbic.201900615

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title = "Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119",

abstract = "The acyl-binding UNC119 proteins mediate the activation and transport of various N-myristoylated proteins. In particular, UNC119a plays a crucial role in the completion of cytokinesis. Herein, we report the use of a lipidated peptide originating from the UNC119 binding partner Gnat1 as the basis for the design of lipidated, stabilized α-helical peptides that target UNC119a. By using the hydrocarbon peptide-stapling approach, cell-permeable binders of UNC119a were generated that induced the accumulation of cytokinetic and binucleated cells; this suggests UNC119a as a potential target for the inhibition of cytokinesis.",

keywords = "alpha-helixes, macrocyclization, peptidomimetics, protein–protein interaction, trafficking",

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doi = "10.1002/cbic.201900615",

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T1 - Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119

AU - Cromm, Philipp M.

AU - Adihou, Hélène

AU - Kapoor, Shobhna

AU - Vazquez-Chantada, Mercedes

AU - Davey, Paul

AU - Longmire, David

AU - Hennes, Elisabeth

AU - Hofer, Walter

AU - Küchler, Philipp

AU - Chiarparin, Elisabetta

AU - Waldmann, Herbert

AU - Grossmann, Tom N.

PY - 2019/12/13

Y1 - 2019/12/13

N2 - The acyl-binding UNC119 proteins mediate the activation and transport of various N-myristoylated proteins. In particular, UNC119a plays a crucial role in the completion of cytokinesis. Herein, we report the use of a lipidated peptide originating from the UNC119 binding partner Gnat1 as the basis for the design of lipidated, stabilized α-helical peptides that target UNC119a. By using the hydrocarbon peptide-stapling approach, cell-permeable binders of UNC119a were generated that induced the accumulation of cytokinetic and binucleated cells; this suggests UNC119a as a potential target for the inhibition of cytokinesis.

AB - The acyl-binding UNC119 proteins mediate the activation and transport of various N-myristoylated proteins. In particular, UNC119a plays a crucial role in the completion of cytokinesis. Herein, we report the use of a lipidated peptide originating from the UNC119 binding partner Gnat1 as the basis for the design of lipidated, stabilized α-helical peptides that target UNC119a. By using the hydrocarbon peptide-stapling approach, cell-permeable binders of UNC119a were generated that induced the accumulation of cytokinetic and binucleated cells; this suggests UNC119a as a potential target for the inhibition of cytokinesis.

KW - alpha-helixes

KW - macrocyclization

KW - peptidomimetics

KW - protein–protein interaction

KW - trafficking

UR - https://www.scopus.com/pages/publications/85075214346

UR - https://www.scopus.com/pages/publications/85075214346#tab=citedBy

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DO - 10.1002/cbic.201900615

M3 - Article

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VL - 20

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EP - 2990

JO - ChemBioChem

JF - ChemBioChem

IS - 24

ER -

Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119

Abstract

Funding

Keywords

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