Exploration of the Binding Mechanism of Cyclic Dinucleotide Analogs to Stimulating Factor Proteins and the Implications for Subsequent Analog Drug Design
Shu-Wei Yuan,
Hong-Ling Shi,
Mu-Ran Fu,
Xi-Chuan Zhang,
Xiao-Qi Xi,
Yao Wang,
Tai-Song Shen,
Jin-Liang Ma,
Cun-Duo Tang
Affiliations
Shu-Wei Yuan
Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China
Hong-Ling Shi
Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China
Mu-Ran Fu
Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China
Xi-Chuan Zhang
Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China
Xiao-Qi Xi
Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China
Yao Wang
Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China
Tai-Song Shen
Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China
Jin-Liang Ma
Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, 46 Jianshe East Road, Xinxiang 453007, China
Cun-Duo Tang
Henan Provincial Engineering Laboratory of Insect Bio-Reactor and College of Life Science and Agricultural Engineering, Nanyang Normal University, 1638 Wolong Road, Nanyang 473061, China
Cyclic dinucleotides (CDNs) are cyclic molecules consisting of two nucleoside monophosphates linked by two phosphodiester bonds, which act as a second messenger and bind to the interferon gene stimulating factor (STING) to activate the downstream signaling pathway and ultimately induce interferon secretion, initiating an anti-infective immune response. Cyclic dinucleotides and their analogs are lead compounds in the immunotherapy of infectious diseases and tumors, as well as immune adjuvants with promising applications. Many agonists of pathogen recognition receptors have been developed as effective adjuvants to optimize vaccine immunogenicity and efficacy. In this work, the binding mechanism of human-derived interferon gene-stimulating protein and its isoforms with cyclic dinucleotides and their analogs was theoretically investigated using computer simulations and combined with experimental results in the hope of providing guidance for the subsequent synthesis of cyclic dinucleotide analogs.
