Princeton University Library Catalog

Construction of Fusion Lasso Peptides with Pharmaceutically-Relevant Sequences

Author/​Artist:
Hubbell, Kenneth Tyler [Browse]
Format:
Senior thesis
Language:
English
Advisor(s):
Link, A. James [Browse]
Department:
Princeton University. Department of Chemical and Biological Engineering [Browse]
Class year:
2016
Description:
53 pages
Summary note:
The promise of small, potent peptide drugs is currently limited by the vulnerability of peptides to proteolysis in the human body. This work demonstrates the potential of highly stable lasso peptides to serve as “scaffolds” for pharmaceutically-relevant sequences. The unique structure of lasso peptides grants them natural resistance to thermal, chemical, and enzymatic degradation, but the maturation enzymes which form this structure are highly sensitive to alterations in the lasso precursor sequence. Previous work had found that the lasso astexin-1 may form even when fused to the leucine zipper A1. Present work expanded on that system to introduce the pharmaceutically-attractive VEGF-binding sequence IHVMWEWECFERL into a disulfide-constrained loop in the tail of astexin-1. The resulting fusion peptide was found to bind VEGF.