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Review
. 2023 Jul;43(4):775-828.
doi: 10.1002/med.21936. Epub 2023 Jan 29.

Design, synthesis, and applications of ring-functionalized histidines in peptide-based medicinal chemistry and drug discovery

Komal Sharma  1 , Krishna K Sharma  1 , Amit Mahindra  1 , Naina Sehra  1 , Nitin Bagra  1 , Shams Aaghaz  1 , Rajesh Parmar  1 , Gajanan K Rathod  1 , Rahul Jain  1
Affiliations
Review

Design, synthesis, and applications of ring-functionalized histidines in peptide-based medicinal chemistry and drug discovery

Komal Sharma et al. Med Res Rev. 2023 Jul.

Abstract

Modified and synthetic α-amino acids are known to show diverse applications. Histidine, which possesses numerous applications when subjected to synthetic modifications, is one such amino acid. The utility of modified histidines varies widely from remarkable biological activities to catalysis, and from nanotechnology to polymer chemistry. This renders histidine residue an important place in scientific research. Histidine is a well-studied scaffold and constitutes the active site of various enzymes catalyzing important reactions in the biological systems. A rational modification in histidine structure with a distinctly developed protocol extensively changes its physical and chemical properties. The utilization of modified histidines in search of potent, target selective and proteostable scaffolds is vital in the development of bioactive peptides with enhanced drug-likeliness. This review is a compilation and analysis of reported side-chain ring modifications at histidine followed by applications of ring-modified histidines in the synthesis of various categories of bioactive peptides and peptidomimetics.

Keywords: CNS active peptides; amino acid functionalization; antimicrobial peptides; functionalized histidines; synthetic peptides.

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References

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