Detalle de: In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF165 neutralization
| Title | In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF165 neutralization |
| Abstract |
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. |
| Apa Reference | Millán-Gómez, D., Dueñas, S., Muñoz, P.L., Camacho-Villegas, T., Elosua, C., Cabanillas-Bernal, O., Escalante, T., Perona, A., Abia, D., Drescher, F., Fournier, P.G., Ramos, M.A., Mares, R.E., Paniagua-Solis, J., Mata-Gonzalez, T., Gonzalez-Canudas, J., Hoffman, R.M., Licea-Navarro, A. & Sánchez-Campos, N. (2018). In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF165 neutralization. Oncotarget, 9(46), 28016-28029. 10.18632/oncotarget.25549 |
| Doi | 10.18632/oncotarget.25549 |
| Publication Date | 15 Jun 2018 |
| Publication Type | Article |
| Researcher | David Ángel Abia Holgado |
| Ontology | Computational models and simulations, Mutation Analysis and design |
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