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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
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.
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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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