Design of a Collagen-Mimetic Peptide for Dynamic Template-Directed Polymerization Open Access

Davis, Griffin (Spring 2022)

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Dynamic chemical networks have been integral in developing the remarkable complexity of life, with the resulting bottom-up process of chemical evolution giving way to the selection, propagation, and diversification of modern biopolymers. Throughout this process, template-directed polymerization has allowed the accurate storage and propagation of molecular information with high fidelity. Combining dynamic polymerization with cross-beta peptide architectures, templates have been shown to direct amplification of chain-length-specific oligomers (which are limited in length by the beta-sheet template). Here, we set out to adapt a dynamic chemical network that would direct the propagation and amplification of a collagen-mimetic peptide that is far more extended than those produced in the established cross-beta system. Self-assembly of the C-terminal peptide aldehyde NPG has been characterized to a certain degree, but much remains unknown about its supramolecular structure. In this work, we develop a reliable protocol for the synthesis of H2N-NPG-CHO monomers and examine ways to tune self-assembly via external templating. The template peptide sequence Ac-(EOGPOG)3EOG-NH2 was synthesized and purified, and its templating ability was evaluated using computational modeling of resulting assemblies. This template is shown to promote triple helix character when self-assembled and form favorable salt bridges with oligomers of NPG, but further analysis is necessary to determine whether the resulting assembly is stable. Further adaptation of this workflow will allow for preliminary analysis of proposed peptide sequences such that promising templates may be investigated experimentally. In this way, external templating of NPG self-assembly builds on pathways for the production of chain-length specific oligomers and models Nature’s ability to direct chemical evolution through template selection.

Table of Contents

1) Introduction (1)

2) Methods (6)

3) Results (10)

4) Discussion (14)

5) Conclusion (27)

6) References (28)

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