Reprogramming natural proteins using unnatural amino acids

Anup Adhikari; Bibek Raj Bhattarai; Ashika Aryal; Niru Thapa; Puja KC; Ashma Adhikari; Sushila Maharjan; Prem B. Chanda; Bishnu P. Regmi; Niranjan Parajuli

doi:10.1039/D1RA07028B

Reprogramming natural proteins using unnatural amino acids

Anup Adhikari,

†^a Bibek Raj Bhattarai,

†^a Ashika Aryal,

^b Niru Thapa,

^a Puja KC,

^a Ashma Adhikari,

^a Sushila Maharjan,

^a Prem B. Chanda,

^c Bishnu P. Regmi

^d and Niranjan Parajuli

*^a

Author affiliations

* Corresponding authors

^a Biological Chemistry Lab, Central Department of Chemistry, Tribhuvan University, Kritipur, Kathmandu, Nepal
E-mail: niranjan.parajuli@cdc.tu.edu.np

^b Department of Chemistry, Birendra Multiple Campus, Tribhuvan University, Bharatpur, Chitwan, Nepal

^c Department of Chemistry and Physics, Southeastern Louisiana University, Hammond, Louisiana 70402, USA

^d Department of Chemistry, Florida Agricultural and Mechanical University, Tallahassee, Florida 32307, USA

Abstract

Unnatural amino acids have gained significant attention in protein engineering and drug discovery as they allow the evolution of proteins with enhanced stability and activity. The incorporation of unnatural amino acids into proteins offers a rational approach to engineer enzymes for designing efficient biocatalysts that exhibit versatile physicochemical properties and biological functions. This review highlights the biological and synthetic routes of unnatural amino acids to yield a modified protein with altered functionality and their incorporation methods. Unnatural amino acids offer a wide array of applications such as antibody-drug conjugates, probes for change in protein conformation and structure–activity relationships, peptide-based imaging, antimicrobial activities, etc. Besides their emerging applications in fundamental and applied science, systemic research is necessary to explore unnatural amino acids with novel side chains that can address the limitations of natural amino acids.

This article is part of the themed collection: 2021 Reviews in RSC Advances

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Reprogramming natural proteins using unnatural amino acids

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