Chemistry Reference
In-Depth Information
(a)
Copper-catalyzed azide-alkyne cycloaddition (CuAAC)
N
R
1
N
Cu(I)
N
R
2
R
1
N
N
N
R
2
triazole
azide
alkyne
(b)
Staudinger ligation
O
O
P
P
R
1
R
1
N
N
R
2
R
2
O
H
OH
N
O
phosphine
phosphine
byproduct
azide
amide
(c)
Copper-free azide-alkyne cycloaddition
N
R
1
N
N
R
1
N
N
N
R
2
R
2
cyclooctyne
azide
triazole
FIGURE 4.1
Bioorthogonal reactions that have been developed for the selective derivatiza-
tion of tagged biomolecules.
the massive diversity of molecules that arise from subtle variations in structure, and
the complexities associated with the environments of cellular membranes.
In order to overcome these obstacles for understanding and mimicking lipid func-
tion, the concept of click chemistry has proven to be an invaluable tool [13]. Click
chemistry has been the subject of numerous recent reviews [14-17], including those
focused on specific areas that this chemistry has impacted, such as bioorthogonal
labeling studies [18-20], medicinal chemistry [17, 21, 22], supramolecular chem-
istry [23], and materials science [24, 25]. Therefore, we will only briefly introduce
the basic principles of this topic herein. In 2002, Sharpless and coworkers outlined
the strategy of click chemistry, which involved the development of reactions that
would proceed rapidly in high yields under ambient conditions to a single desired
product through the reaction of readily available functional groups, and in doing so
tolerate the presence of a range of functional groups on the starting materials [26].
The prototypical click reaction was the copper-catalyzed azide-alkyne cycloaddition
(CuAAC, Fig. 4.1a)—a modification to the original 1,3-dipolarcycloaddition reported
by Huisgen [27]—that was reported concurrently by both Sharpless and coworkers
[28], as well as Meldal and coworkers [29].
One of the key advantages of CuAAC is that the azide and alkyne reactive
partners employed for this reaction are orthogonal to biological systems, since
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