Date of Award


Document Type



Santa Clara : Santa Clara University, 2016.



First Advisor

Zhiwen Zhang


Described herein is a novel workflow for the synthesis of engineered peptide biomolecules that mimic the function and activity of monoclonal antibodies. The technique uses computational design and unnatural amino acid chemistry to deliver a comparable alternative to monoclonal antibodies. The software package Chimera8, developed at UCSF for molecular visualization and open-source for academic licenses, was used to select hits from a library of peptides that had strong predicted binding to disease biomarkers. Each candidate peptide was scored based on electrostatic interactions with the target and ranked in order of predicted binding affinity.

The top hits were then engineered to include an l-DOPA unnatural amino acid as described previously10, which will form a covalent link to the target biomarker upon oxidation. The engineered peptide was then recombinantly expressed and purified from E. coli cell culture. The resulting synthetic antibody achieves target specificity from the peptide backbone and affinity from the covalent cross-linker, which rivals the specificity and affinity of traditional monoclonal antibodies. This technology presents an alternative to monoclonal antibody production, avoiding outsourced and intensive production and quality control.