Homology modeling,molecular docking and site-directed mutagenesis of a human disulfide-stabilized diabody against fibroblast growth factor-2
The human fibroblast growth factor-2(FGF-2)is a key factor in promoting tumor lymphangiogensis and angiogenesis.Disulfide-stabilized diabody(ds-Diabody)against FGF-2 can inhibit tumor angiogenesis and growth.We improved the affinity of ds-Diabody against FGF-2 by computational homology modeling,molecular docking,site-directed mutagenesis and binding experiments,including the construction,the secretory expression of mutated ds-Diabody against FGF-2 proteins in HEK293T cells and the binding of mutated ds-Diabody against FGF-2 to FGF-2 by ELISA(all the computational calculations were made with Discovery StudioTM 4.5).The mutated ds-Diabody against FGF-2 shows its higher binding activity with 17 mutated amino acid residues(17 residues include Asn-37>Trp,Asp-56>Glu,Ser-105>Glu,Ser-109>Glu,Ser-114>His,Val-116>Trp,Thr-229>Asp,Ser-236>Tyr,Glu-238>His,Ile-256>Phe,Ser-258>His,Ser-259>Trp,Ser-263>Phe,Thr-264>Glu,Glu-307>Leu,Thr-309>Tyr,Asp-311>Phe).The research results were helpful to develop a promising antibody-based drug in cancer therapeutics.
Simin Zhang Jiangchuan Zhong Ning Deng
Guangdong Province Engineering Research Center for antibody drug and immunoassay,Department of Biology,Jinan University,Guangzhou 510632,China
国内会议
第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)
太原
英文
407-410
2018-05-01（万方平台首次上网日期，不代表论文的发表时间）