Facets of click-mediated triazoles in decorating amino acids and peptides

Abstract

Decorating biomolecular building blocks, such as amino acids, to afford desired and tuneable photophysical/biophysical properties would allow chemical biologists to use them for several biotechnological and biosensing applications. While many synthetic methodologies have been explored in this direction, advantages provided by click-derived triazole moieties are second to none. However, since their discovery, click-mediated triazoles have been majorly utilised as linkers for conjugating biomolecules, creating materials with novel properties, such as polymers or drug conjugates. Despite exploring their profound role as linkers, click-mediated triazoles as an integral part of biomolecular building blocks have not been addressed. 1,2,3-Triazole, a transamide mimic, exhibits high aromatic stacking propensity, high associability with biomolecules through H-bonding, and high stability against enzymatic hydrolysis. Furthermore, triazoles can be considered donors useable for installation/modulation of the photophysics of a fluorophore. Therefore, triazole with a chromophoric unit may rightly be utilised as an integral part of biomolecular building blocks to install microenvironment-sensitive solvofluorochromic properties suitable for biological sensing, studying inter-biomolecular interactions and introducing novel physicochemical properties in a biomolecule. This review mainly focuses on the facets of click-derived triazole in designing novel fluorescent amino acids and peptides with a particular emphasis on those wherein triazole acts as an integral part of amino acids, i.e. the side chain, generating a new class of fluorescent unnatural triazolyl amino acids. Thus, fluorescent triazolyl unnatural amino acids, peptidomimetics with such amino acids and aliphatic/aromatic triazolyl amino acids as scaffolds for peptidomimetics are the central part. However, to start with, a brief history, followed by a discussion on various other relevant facets of triazoles as linkers in various fields ranging from therapeutics, materials science, diagnostics, and bioconjugation to peptidomimetics, is cited. Additionally, the possible roles of CuAAC-mediated triazoles in shaping the future of bioorganic chemistry, medicinal chemistry, diagnostics, nucleoside chemistry and protein engineering are briefly discussed.