Serine-mediated hydrazone ligation displaying insulin-like peptides on M13 phage pIII

Zhang, Yi Wolf; Zheng, Nan; Chou, Danny Hung-Chieh

doi:10.1039/d3ob01487h

Cited by 1 publication

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“…We also demonstrated that omniligase-1 could specifically mediate the ligation of substrates to phage pIII protein with high efficiency and conversion rate while not targeting other phage coat proteins. This new approach circumvents the need for specific epitopes on phage, as required by Sortase A, or chemical modifications, , thereby expanding the substrate scope and enhancing the diversity of phage display libraries. Our two-chain insulin phage display system enabled the rapid construction of a highly diverse insulin library within 24 h. Through the screening of this library against IR, we identified several new insulin ligands from randomized sequences that displayed activity comparable to hIns.…”

Section: Discussionmentioning

confidence: 99%

Section: ■ Conclusionmentioning

confidence: 99%

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Omniligase-1-Mediated Phage-Peptide Library Modification and Insulin Engineering

Zhang,

Lin,

Guo

et al. 2024

ACS Chem. Biol.

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Chemical and enzymatic modifications of peptide-displayed libraries have been successfully employed to expand the phage display library. However, the requirement of specific epitopes and scaffolds has limited the scope of protein engineering using phage display. In this study, we present a novel approach utilizing omniligase-1-mediated selective and specific ligation on the phage pIII protein, offering a high conversion rate and compatibility with commercially available phage libraries. We applied this method to perform high-throughput engineering of insulin analogues with randomized B chain C-terminal regions. Insulin analogues with different B chain C-terminal segments were selected and exhibited biological activity equivalent to that of human insulin. Molecular dynamics studies of insulin analogues revealed a novel interaction between the insulin B27 residue and insulin receptor L1 domain. In summary, our findings highlight the potential of omniligase-1-mediated phage display in the development and screening of disulfide-rich peptides and proteins. This approach holds promise for the creation of novel insulin analogues with enhanced therapeutic properties and exhibits potential for the development of other therapeutic compounds.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Conclusionmentioning

confidence: 99%

Omniligase-1-Mediated Phage-Peptide Library Modification and Insulin Engineering

Zhang,

Lin,

Guo

et al. 2024

ACS Chem. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

Serine-mediated hydrazone ligation displaying insulin-like peptides on M13 phage pIII

Abstract: Phage display has emerged as a tool for the discovery of therapeutic antibodies and proteins. However, the effective display and engineering of structurally complex proteins, such as insulin, pose significant...

Cited by 1 publication

References 54 publications

Omniligase-1-Mediated Phage-Peptide Library Modification and Insulin Engineering

Omniligase-1-Mediated Phage-Peptide Library Modification and Insulin Engineering

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