1 research outputs found
Omniligase-1-Mediated Phage-Peptide Library Modification and Insulin Engineering
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