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Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1

Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) fami...

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Autores principales: Luptak, Jakub, Bista, Michal, Fisher, David, Flavell, Liz, Gao, Ning, Wickson, Kate, Kazmirski, Steven L., Howard, Tina, Rawlins, Philip B., Hargreaves, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834078/
https://www.ncbi.nlm.nih.gov/pubmed/31692474
http://dx.doi.org/10.1107/S2059798319014116
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author Luptak, Jakub
Bista, Michal
Fisher, David
Flavell, Liz
Gao, Ning
Wickson, Kate
Kazmirski, Steven L.
Howard, Tina
Rawlins, Philip B.
Hargreaves, David
author_facet Luptak, Jakub
Bista, Michal
Fisher, David
Flavell, Liz
Gao, Ning
Wickson, Kate
Kazmirski, Steven L.
Howard, Tina
Rawlins, Philip B.
Hargreaves, David
author_sort Luptak, Jakub
collection PubMed
description Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.
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spelling pubmed-68340782019-11-15 Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1 Luptak, Jakub Bista, Michal Fisher, David Flavell, Liz Gao, Ning Wickson, Kate Kazmirski, Steven L. Howard, Tina Rawlins, Philip B. Hargreaves, David Acta Crystallogr D Struct Biol Research Papers Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design. International Union of Crystallography 2019-10-31 /pmc/articles/PMC6834078/ /pubmed/31692474 http://dx.doi.org/10.1107/S2059798319014116 Text en © Luptak et al. 2019 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Papers
Luptak, Jakub
Bista, Michal
Fisher, David
Flavell, Liz
Gao, Ning
Wickson, Kate
Kazmirski, Steven L.
Howard, Tina
Rawlins, Philip B.
Hargreaves, David
Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1
title Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1
title_full Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1
title_fullStr Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1
title_full_unstemmed Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1
title_short Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1
title_sort antibody fragments structurally enable a drug-discovery campaign on the cancer target mcl-1
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834078/
https://www.ncbi.nlm.nih.gov/pubmed/31692474
http://dx.doi.org/10.1107/S2059798319014116
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