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Serine-mediated hydrazone ligation displaying insulin-like peptides on M13 phage pIII.
- Source :
-
Organic & biomolecular chemistry [Org Biomol Chem] 2023 Nov 15; Vol. 21 (44), pp. 8902-8909. Date of Electronic Publication: 2023 Nov 15. - Publication Year :
- 2023
-
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 challenges due to the sequence of insulin, which is composed of two peptide chains linked by three disulfide bonds. In this study, we developed a new approach for the display of insulin-like peptides on M13 phage pIII, employing N-terminal serine-mediated hydrazone ligation. The insulin-displaying phage retains the biological binding affinity of human insulin. To address the viability loss after ligation, we introduced a trypsin-cleavable spacer on pIII, enabling insulin-displayed phage library selection. This method offers a general pathway for the display of structurally complex proteins on pIII, enhancing the practicality of selecting chemically modified phage libraries and opening avenues for the engineering of new insulin analogs for the treatment of diabetes by using phage display.
Details
- Language :
- English
- ISSN :
- 1477-0539
- Volume :
- 21
- Issue :
- 44
- Database :
- MEDLINE
- Journal :
- Organic & biomolecular chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 37905463
- Full Text :
- https://doi.org/10.1039/d3ob01487h