Defense Date

2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Matthew C.T Hartman

Abstract

Peptide macrocyclization has been employed to improve peptide pharmacological features like binding affinity; nevertheless, although generic, this approach is not fully proven, and some exceptions to the rule have been observed. In this work, we addressed such a trend by comparing peptide libraries of different cyclization orders (linear, monocyclic, and bicyclic) to their binding affinity distribution towards a model target to answer if cyclization improves binding affinity unambiguously. From another perspective, several hundreds of cyclization strategies allow peptides to adopt different topologies and use fancy linkers with a wide range of reaction conditions; nevertheless, a couple of those are compatible with display technologies that enable the screening of billions of compounds in one pot. In this work, we introduced two novel non-canonical amino acids, pCAF and pCPF, that are compatible with in vitro translation systems and that allows flexible, stable, spontaneous, selective, and efficient peptide macrocyclization and that can be incorporated into mRNA display systems and have potential to decrease operational work. References

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-11-2022

Available for download on Tuesday, August 10, 2027

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