Custom Synthesis of Strained Cyclooctyne-‐Peptide Conjugates for Copper-‐Free Click Chemistry Copper catalyzed azide alkyne cycloaddition (CuAAC) is an exceptional example of “click chemisty” which offers wide range of applications in chemical biology and materials science. Although CuAAC applications have grown tremendously, the requirement of a cytotoxic copper catalyst limits its applications in biological systems such as imaging proteins and other biomolecule labelling within living cells and animals. Addressing this issue, in recent years, the concept “strain promoted azide alkyne cycloaddition” (SPAAC) has been introduced where the strain in eight-‐membered cyclooctyne ring allows the reaction with azides to occur in the absence of cytotoxic Copper. Figure 1: Cu free click chemistry ligation strategy Several structurally varied cyclooctyne analogs have been studied for SPAAC reaction to improve their stability, selectivity and reaction kinetics (Figure 2). Figure 2: Examples of cyclooctynes for SPAAC Among the several cyclooctynes developed, diarylcyclooctynes reagents (DBCO & DIBO) are widely used for this emerging biorthogonal ligation strategy. These reagents are thermostable with specific reactivity towards azides resulting in almost quantitative yield of single, stable triazole isomer. Peptides International offers custom synthesis of peptide/protein conjugates with DBCO, azide or other specific reagent of customer’s interest. We can also synthesize DBCO-‐fluorscent dye conjugates of your interest which can be efficiently used for the detection of azides over a wide range of biorthogonal reporter applications. Figure 3: Examples of DBCO reagents to conjugate with peptide/protein
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