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DNA Framework Programmed Conformational Reconstruction of Antibody Complementary Determining Region

[Image: see text] The conformation of complementary determining region (CDR) is crucial in dictating its specificity and affinity for binding with an antigen, making it a focal point in artificial antibody engineering. Although desirable, programmable scaffolds that can regulate the conformation of...

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Detalles Bibliográficos
Autores principales: Zhou, Liqi, Ren, Lei, Bai, Zhiang, Xia, Qinglin, Wang, Yue, Peng, Hongzhen, Yan, Qinglong, Shi, Jiye, Li, Bin, Guo, Linjie, Wang, Lihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598557/
https://www.ncbi.nlm.nih.gov/pubmed/37885585
http://dx.doi.org/10.1021/jacsau.3c00492
Descripción
Sumario:[Image: see text] The conformation of complementary determining region (CDR) is crucial in dictating its specificity and affinity for binding with an antigen, making it a focal point in artificial antibody engineering. Although desirable, programmable scaffolds that can regulate the conformation of individual CDRs with nanometer precision are still lacking. Here, we devise a strategy to program the CDR conformation by anchoring both ends of a free CDR loop to specific sites of a DNA framework structure. This method allows us to define the span of a single CDR loop with an ∼2 nm resolution. Using this approach, we create a series of DNA framework based artificial antibodies (DNFbodies) with varied CDR loop spans, leading to different antibody–antigen binding affinities. We find that an optimized single CDR loop (∼2.3 nm span) exhibits ∼3-fold improved affinity relative to natural antibodies, confirming the critical role of the CDR conformation. This study may inspire the rational design of artificial antibodies.