Application of the 1,3‐Dipolar Cycloaddition Reaction in Chemical Biology: Approaches Toward Multivalent Carbohydrates and Peptides and Peptide‐Based Polymers

Abstract

In this mini review we highlight our recent results and the related literature regarding the application of the Cu(I)-catalyzed 1,3-dipolar cycloaddition "click" reaction. The synthetic applications of the click reaction focus on multivalent carbohydrates and peptides and peptide-based polymers. Furthermore, a related reaction is described involving the coupling of thio acids and sulfonyl azides leading to the chemoselective formation of amides.

Click Chemistry: A Powerful Tool to Create Polymer‐Based Macromolecular Chimeras

“…Among these, the copper (I) catalyzed variant [2,3] of the Huisgen 1,3-dipolar cycloaddition [4][5][6] (CuAAC, Scheme 1) has certainly been the ''cream of the crop'' of click reactions, so much that it is now often referred to as the ''click chemistry reaction.'' Several reports have confirmed the wealth of applications of this practical and sensible chemical approach in the areas of bioconjugation, [7][8][9][10] polymer and materials sciences [11][12][13][14] and drug discovery. [15] The present review aims at summarizing the latest discoveries in the area of polymer bioconjugation using the azide-alkyne ''click'' chemistry (Scheme 1).…”

Polymer “Clicking” by CuAAC Reactions

“…Read and Ames [22] described the use of CuAAC ''clicking'' in the synthesis of cross linked micelles. A relatively new polymer area of CuAAC that has only been briefly reviewed by Spain et al, [23] Pieters et al [24] and Dirks et al [25] is that of combining traditional polymers with biopolymers. Lecomte et al [26] reviewed functionalization strategies for polycaprolactones.…”

Membrane Permeabilization by Multivalent Anti-Microbial Peptides

“…In order to further enhance the pore forming abilities of magainin, in our laboratories we prepared multivalent versions of it in an at- tempt to bypass the limiting assembly process mentioned above [29]. Dendrimers based on the 3,5-di-(2-aminoethoxy)-benzoic acid repeating unit [30] were used and outfitted with alkyne groups to allow 'click' chemistry [31][32][33] for conjugation of the peptides to the dendrimers. The magainin peptides were outfitted with an azide functionality via the incorporation of a modified lysine amino acid containing an azide instead of the -amino group [34].…”

“…The magainin peptides were outfitted with an azide functionality via the incorporation of a modified lysine amino acid containing an azide instead of the -amino group [34]. Conjugation of the magainin peptides to the dendrimers was achieved via standard "click" reaction conditions [33]. Divalent peptide 20 was thus obtained (Fig.…”