Utilization of Lasso Peptides for the Biomineralization of Calcium Carbonate

Abstract

Peptides are attractive targets for drug design as they can easily be engineered to have therapeutic benefits, but they are usually unstable in the biological systems where they are useful. Lasso peptides, with their unique topology and resistance to enzymatic degradation, offer a solution to this problem. The work here questions whether lasso peptides can be engineered for the purpose of biomineralization. Astexin-1, a lasso peptide that has been previously shown to readily accept fusion proteins, was chosen as a scaffold. An acidic peptide sequence, designed to interact with the surface of calcium carbonate, was engineered on to the C-terminus of astexin-1. Calcium carbonate crystallization experiments were conducted, and three peptides and their ability to mediated crystal growth were compared: astexin-1, the acidic tail, and the newly designed fusion of astexin-1 and the acidic tail. The newly designed peptide not only maintained the function of the acidic tail, but was more efficient at mediating crystal growth. This work suggests that lasso peptides and their stabilizing capabilities can be utilized in the design of new peptides for therapeutic biomineralization and biomimetic materials.