Photocleavable linker methods and compositions
View Patent ↗Bifunctional linkers are provided that comprise a photocleavable moiety flanked by two different amine reactive moieties. In some embodiments the photocleavable moiety is a dimethoxynitrobenzyl moiety. In other embodiments the photocleavable moiety is 8-bromo-7-hydroxyquinoline. In other embodiments the photocleavable moiety is nitrodibenzofuran. In other embodiments the photocleavable moiety is 6-bromo-7-hydroxycoumarin-4-ylmethyl. The linkers find use in synthetic methods, including the generation of photocleavable oligonucleotides, e.g. caged morpholinos.
1. A bifunctional linker having the structure:
where X is a photocleavable moiety;
R1 and R2 are independently selected from succinimide (NHS ester):
isothiocyanate:
propargyl:
iodoacetamide:
maleimide:
azide:
and terminal alkene:
R3, R4 and R5 are independently selected from H and C1-C6 lower alkyls; and
n is an integer from 0 to 10.
2. The linker of claim 1 , wherein X is a UV excited moiety.
3. The linker of claim 2 , wherein X is a 1,2-dimethoxy-4-nitrobenzyl moiety;
or a nitrobenzyl moiety.
4. The linker of claim 1 , wherein X is a multiphoton activated moiety.
5. The linker of claim 4 , wherein X is selected from 6-bromo-7-hydroxycoumarin-4-ylmethyl;
8-bromo-7-hydroxyquinolinyl;
or a nitrodibenzofuran moiety