化学
DNA
三聚体
肽
螺旋线圈
蛋白质折叠
蛋白质工程
结构母题
计算生物学
折叠(DSP实现)
生物化学
酶
生物
二聚体
有机化学
电气工程
工程类
作者
Fei Zhao,Martin Frandsen,Sabrina Capodaglio,Hanadi F. Sleiman
摘要
The design of new protein structures is challenging due to their vast sequence space and the complexity of protein folding. Here, we report a new modular DNA-templated strategy to construct protein mimics. We achieve the spatial control of multiple peptide units by conjugation with DNA and hybridization to a branched DNA trimer template followed by covalent stapling of the preorganized peptides into a single unit. A library of protein mimics with different lengths, sequences, and heptad registers has been efficiently constructed. DNA-templated protein mimics show an α-helix or coiled-coil motif formation even when they are constructed from weakly interacting peptide units. Their attached DNA handles can be used to exert dynamic control over the protein mimics' secondary and tertiary structures. This modular strategy will facilitate the development of DNA-encoded protein libraries for the rapid discovery of new therapeutics, enzymes, and antibody mimics.
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