Synthesis of hexaphenylbenzene-based template assembled synthetic proteins

Madhu, Suresh; Madica, Krishnaprasad; Gonnade, Rajesh; Sanjayan, Gangadhar J.

doi:10.1016/j.tetlet.2019.07.011

Cited by 1 publication

(1 citation statement)

References 38 publications

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“…For spontaneous coiled-coil formation, three or more heptad repeats (>21 amino acids) are usually required to provide enough stabilization from peptide–peptide interactions . Coiled-coil motifs can be assembled from de novo designed peptide fragments , and can be further stabilized via the chelation of metal ions, covalent linking, or stapling with organic molecules. − Additionally, peptide–peptide interactions can be stabilized by combining them with supramolecular templating effects, where template-assembled synthetic proteins (TASPs) have been shown to facilitate the production of complex protein structures. − Nevertheless, with their symmetric nature, most TASPs can produce only homomeric helix bundles. Arora et al have overcome the canonical coiled-coil length limit by constructing coiled-coil mimics from two-heptad α-helices using linear organic synthesis. − …”

Section: Introductionmentioning

confidence: 99%

DNA-Mediated Peptide Assembly into Protein Mimics

Zhao,

Frandsen,

Capodaglio

et al. 2024

J. Am. Chem. Soc.

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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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