In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF(165) neutralization
The stability, binding, and tissue penetration of variable new-antigen receptor (VNAR) single-domain antibodies have been tested as part of an investigation into their ability to serve as novel therapeutics. V13 is a VNAR that recognizes vascular endothelial growth factor 165 (VEGF(165)). In the pre...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021326/ https://www.ncbi.nlm.nih.gov/pubmed/29963259 http://dx.doi.org/10.18632/oncotarget.25549 |
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author | Millán-Gómez, Dalia Dueñas, Salvador Muñoz, Patricia L. A. Camacho-Villegas, Tanya Elosua, Carolina Cabanillas-Bernal, Olivia Escalante, Teresa Perona, Almudena Abia, David Drescher, Florian Fournier, Pierrick G. J. Ramos, Marco A. Mares, Rosa E. Paniagua-Solis, Jorge Mata-Gonzalez, Teresa Gonzalez-Canudas, Jorge Hoffman, Robert M. Licea-Navarro, Alexei Sánchez-Campos, Noemí |
author_facet | Millán-Gómez, Dalia Dueñas, Salvador Muñoz, Patricia L. A. Camacho-Villegas, Tanya Elosua, Carolina Cabanillas-Bernal, Olivia Escalante, Teresa Perona, Almudena Abia, David Drescher, Florian Fournier, Pierrick G. J. Ramos, Marco A. Mares, Rosa E. Paniagua-Solis, Jorge Mata-Gonzalez, Teresa Gonzalez-Canudas, Jorge Hoffman, Robert M. Licea-Navarro, Alexei Sánchez-Campos, Noemí |
author_sort | Millán-Gómez, Dalia |
collection | PubMed |
description | The stability, binding, and tissue penetration of variable new-antigen receptor (VNAR) single-domain antibodies have been tested as part of an investigation into their ability to serve as novel therapeutics. V13 is a VNAR that recognizes vascular endothelial growth factor 165 (VEGF(165)). In the present study V13 was used as a parental molecule into which we introduced mutations designed in silico. Two of the designed VNAR mutants were expressed, and their ability to recognize VEGF(165) was assessed in vitro and in vivo. One mutation (Pro98Tyr) was designed to increase VEGF(165) recognition, while the other (Arg97Ala) was designed to inhibit VEGF(165) binding. Compared to parental V13, the Pro98Tyr mutant showed enhanced VEGF(165) recognition and neutralization, as indicated by inhibition of angiogenesis and tumor growth. This molecule thus appears to have therapeutic potential for neutralizing VEGF(165) in cancer treatment. |
format | Online Article Text |
id | pubmed-6021326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-60213262018-06-30 In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF(165) neutralization Millán-Gómez, Dalia Dueñas, Salvador Muñoz, Patricia L. A. Camacho-Villegas, Tanya Elosua, Carolina Cabanillas-Bernal, Olivia Escalante, Teresa Perona, Almudena Abia, David Drescher, Florian Fournier, Pierrick G. J. Ramos, Marco A. Mares, Rosa E. Paniagua-Solis, Jorge Mata-Gonzalez, Teresa Gonzalez-Canudas, Jorge Hoffman, Robert M. Licea-Navarro, Alexei Sánchez-Campos, Noemí Oncotarget Research Paper The stability, binding, and tissue penetration of variable new-antigen receptor (VNAR) single-domain antibodies have been tested as part of an investigation into their ability to serve as novel therapeutics. V13 is a VNAR that recognizes vascular endothelial growth factor 165 (VEGF(165)). In the present study V13 was used as a parental molecule into which we introduced mutations designed in silico. Two of the designed VNAR mutants were expressed, and their ability to recognize VEGF(165) was assessed in vitro and in vivo. One mutation (Pro98Tyr) was designed to increase VEGF(165) recognition, while the other (Arg97Ala) was designed to inhibit VEGF(165) binding. Compared to parental V13, the Pro98Tyr mutant showed enhanced VEGF(165) recognition and neutralization, as indicated by inhibition of angiogenesis and tumor growth. This molecule thus appears to have therapeutic potential for neutralizing VEGF(165) in cancer treatment. Impact Journals LLC 2018-06-15 /pmc/articles/PMC6021326/ /pubmed/29963259 http://dx.doi.org/10.18632/oncotarget.25549 Text en Copyright: © 2018 Millán-Gómez et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Millán-Gómez, Dalia Dueñas, Salvador Muñoz, Patricia L. A. Camacho-Villegas, Tanya Elosua, Carolina Cabanillas-Bernal, Olivia Escalante, Teresa Perona, Almudena Abia, David Drescher, Florian Fournier, Pierrick G. J. Ramos, Marco A. Mares, Rosa E. Paniagua-Solis, Jorge Mata-Gonzalez, Teresa Gonzalez-Canudas, Jorge Hoffman, Robert M. Licea-Navarro, Alexei Sánchez-Campos, Noemí In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF(165) neutralization |
title | In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF(165) neutralization |
title_full | In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF(165) neutralization |
title_fullStr | In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF(165) neutralization |
title_full_unstemmed | In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF(165) neutralization |
title_short | In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF(165) neutralization |
title_sort | in silico-designed mutations increase variable new-antigen receptor single-domain antibodies for vegf(165) neutralization |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021326/ https://www.ncbi.nlm.nih.gov/pubmed/29963259 http://dx.doi.org/10.18632/oncotarget.25549 |
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