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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2019
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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. |
format | Online Article Text |
id | pubmed-6834078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
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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