Bioinformatics-led design of single-chain antibody molecules targeting DNA sequences for retinoblastoma
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Zhengzhou Municipal Science and Technology Projects of Development,China (No. 0910SGYS33377-1); Projects of Science and Technology Research of Shaanxi Province,China (No. 2007k09-06);the Social Development Project of Xi’an, China (No.YF07164)

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    Abstract:

    AIM: To analyze the relationship between the structure and function of single-chain Fv antibody (scFv) with bioinformatics methods, so as to provide theoretical basis for retinoblastoma targeted therapy. METHODS: Single-chain antibodies are reconstructed for cancer-targeted therapy to provide good penetration into tumor tissue and to improve their pharmacokinetics in vivo, offering a clinically valuable application. The relationship needs to be analyzed that there may be some variations between the structure and function of the fusion proteins, and the relationship between the structure and function of protein molecules was obtained through analyzing relevant literature at home and abroad as well as modeling analysis. RESULTS: Through our analysis of the interaction region between the antibody and the antigen, and of the binding sites for molecular conformation, it is clear that existing antibodies need to be modified at the DNA sequence level, enhancing the biological activity of the antibodies. Based on the view that bio-molecular computer models are closely integrated with biological experiments, a bio-molecular structure–activity relationship model can be established in terms of molecular conformation, physical and chemical properties and the biological activity of single-chain antibodies. Two enlightenments are obtained from our analysis. On the one hand, the structure–activity relationship is clear for new immune molecules at the gene expression level. On the other hand, a single-chain antibody molecule can be designed and optimized for the cancer-oriented treatment. CONCLUSION: In this article, we provide the theoretical and experimental basis for the development of single-chain antibodies appropriate for retinoblastoma therapy.

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Guo-Gang Shang, Jian-Hua Zhang, Yong-Gang Lu, et al. Bioinformatics-led design of single-chain antibody molecules targeting DNA sequences for retinoblastoma. Int J Ophthalmol, 2011,4(1):8-13

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