Utilization of π-cation stabilized β-hairpin for construction of hybrid tertiary structures

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Principal Investigator: Katarzyna Ożga

Project financed by National Science Centre, Miniatura, no 2022/06/X/ST4/00008

Start date: June 1st, 2022

Budget: 49 500 PLN

Abstract

The rational design of molecules of custom three-dimensional structures is gaining a lot of attention. Foldamers and miniproteins are of particular interest because of their synthetic availability with a wide range of building blocks and well-recognized relations between sequence and secondary structure. However, the design of more complex, tertiary, and quaternary structures remains challenging.

There were many attempts to produce folded polypeptides starting from the de novo design to engineering of native folds with noncanonical amino acids. In this project we plan to obtain highly stable hybrid tertiary folds by combining two stable secondary structures: foldameric helix containing cyclic β-amino acids and π-cation-stabilized β-hairpin. The π-cation stabilization, while present in native proteins, was not yet utilized in the design of miniproteins.

The project will be based on repeating rounds of design and optimization of the hydrophobic core and changing the length and connectivity of secondary structures in computationally prepared models and may result in unprecedented new tertiary folds.