Design and synthesis of an all-in-one 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group for photo-affinity labeling.

Abstract:

:A novel radioisotope-free photo-affinity probe containing the 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group was designed and synthesized. This very compact functionality is envisaged to allow photochemically-induced coupling of a compound to its target followed by click reaction coupling with an azido-biotin reagent in order to facilitate purification of the labeled target. In a proof-of-concept study we have shown that 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group could be photolyzed to efficiently furnish the methanol adduct 23 and that the generated highly unstable carbene does not react with the neighboring acetylene moiety. A subsequent click reaction with the azido-biotin derivative 25 proceeded smoothly to give triazole 26. This chemical probe should thus be of unique value for facilitating identification of the molecular structure of the target of a bioactive compound.

journal_name

Bioorg Med Chem

authors

Kumar NS,Young RN

doi

10.1016/j.bmc.2009.06.048

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

5388-95

issue

15

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(09)00611-7

journal_volume

17

pub_type

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