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dc.contributor.authorHaidar, Malak
dc.contributor.authorde Laté, Perle Latré
dc.contributor.authorKennedy, Eileen J.
dc.contributor.authorLangsley, Gordon
dc.date.accessioned2017-09-14T06:03:52Z
dc.date.available2017-09-14T06:03:52Z
dc.date.issued2017-09-08
dc.identifier.citationHaidar M, de Laté PL, Kennedy EJ, Langsley G (2017) Cell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria -transformed leukocytes. Bioorganic & Medicinal Chemistry. Available: http://dx.doi.org/10.1016/j.bmc.2017.08.056.
dc.identifier.issn0968-0896
dc.identifier.pmid28917447
dc.identifier.doi10.1016/j.bmc.2017.08.056
dc.identifier.urihttp://hdl.handle.net/10754/625451
dc.description.abstractOne powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way to explore their contribution to a particular cellular phenotype in a given disease context. Cell-penetrating peptides can be synthetically constrained through various chemical modifications that stabilize a given structural fold with the potential to improve competitive binding to specific targets. Theileria-transformed leukocytes display high PKA activity, but PKAis an enzyme that plays key roles in multiple cellular processes; consequently genetic ablation of kinase activity gives rise to a myriad of confounding phenotypes. By contrast, ablation of a specific kinase-substrate interaction has the potential to give more refined information and we illustrate this here by describing how surgically ablating PKA interactions with BAD gives precise information on the type of glycolysis performed by Theileria-transformed leukocytes. In addition, we provide two other examples of how ablating specific protein-protein interactions in Theileria-infected leukocytes leads to precise phenotypes and argue that constrained penetrating peptides have great therapeutic potential to combat infectious diseases in general.
dc.description.sponsorshipMK and GL acknowledge support from a CRG4 grant [URF/1/2610-01-01] from the Office for Sponsored Research (OSR) in King Abdullah University of Science and Technology (KAUST). PLdL and GL acknowledge support from an ANR-11-LABX-0024 grant and GL core funding from INSERM and the CNRS. EJK acknowledges support by the National Institutes of Health (CA154600 and CA188439).
dc.publisherElsevier BV
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0968089617313172
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Bioorganic & Medicinal Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic & Medicinal Chemistry, [, , (2017-09-08)] DOI: 10.1016/j.bmc.2017.08.056 . © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCell penetrating peptides
dc.subjectTheileria
dc.subjectPKA, BAD, Grb-2
dc.subjectJNK
dc.titleCell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria -transformed leukocytes
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentPathogen Genomics Laboratory
dc.identifier.journalBioorganic & Medicinal Chemistry
dc.eprint.versionPost-print
dc.contributor.institutionLaboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médecine, Université Paris Descartes - Sorbonne Paris Cité, 75014, France
dc.contributor.institutionInserm U1016, Cnrs UMR8104, Cochin Institute, Paris 75014, France
dc.contributor.institutionDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, United States
kaust.personHaidar, Malak
dc.date.published-online2017-09-08
dc.date.published-print2018-03


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