“Click” reactions: a versatile toolbox for the synthesis of peptide-conjugates

Abstract

Peptides that comprise the functional subunits of proteins have been conjugated to versatile materials (biomolecules, polymers, surfaces and nanoparticles) in an effort to modulate cell responses, specific binding affinity and/or self-assembly behavior. However, the efficient and convenient synthesis of peptide-conjugates, especially the constructs with multiple types of peptide functionality remains challenging. In this critical review, we focus on "click" reactions that have been used to synthesis peptide-functionalized conjugates, introducing their reaction conditions, specifically elucidating parameters that influence reaction kinetics and total conversion, and highlighting examples that have been completed recently. Moreover, orthogonal "click" reactions that synthesize multi-functional biomaterials in a one-pot or sequential manner are noted. Through this review, a comprehensive understanding of "click" reactions aims to provide insight on how one might choose suitable "click" reactions to constitute peptide-functionalized molecules/surfaces/matrices for the development of advanced biomaterials.

Dendron conjugation to graphene oxide using click chemistry for efficient gene delivery

“…The use of "click" chemistry offers many advantages for bioconjugation including high specicity with minimal by-products. 27 Importantly, a major limitation of EDC conjugation used previously for PEI modication of GO is the lack of specicity, 12,15,28 which may result in a crosslinked mass of many GO akes conjugated to a single PEI molecule. Such crosslinking can be minimized by "click" chemistry utilized herein.…”

Creating biomaterials with spatially organized functionality

“…Over the past decade, a set of chemical reactions commonly referred to as ''click chemistry'' have been developed that can be performed in the presence of cells without unwanted side reactions with native biomolecules. 17,[60][61][62][63][64] For example, DeForest and Anseth demonstrated that combining two bioorthogonal photochemical reactions, which enabled the reversible spatial presentation of a biological cue, could be performed in the presence of cells to create dynamic, welldefined biochemical gradients within a single hydrogel. 17,63 Non-covalent bioorthogonal chemistries can also be utilized for specific and dynamic methods to organize functionality.…”

Amino acid-incorporated polymer network by thiol-ene polymerization

“…We also reported trehalose-and eugenol-incorpolated polymer networks by thiol-ene photopolymerizations [43,44]. In the past studies, thiol-ene reactions have been applied to the modification of unsaturated amino acids [45] and to the synthesis of peptide-functionalized conjugates [46], but amino acid-based polymer network has not been prepared by use of thiolene polymerization to the best of our knowledge. In this study, triallyl L-alanine (A3A) and triallyl Lphenylalanine (A3F) whose N-and C-terminals are simultaneously modified with allyl groups were conveniently synthesized by one-pot reactions of Lalanine and L-phenylalanine with allyl bromide, respectively (Figure 1), and thermal and mechanical properties of polymer networks prepared by thiol-ene reactions of A3A and A3F with tetrathiol compounds were investigated.…”