Synthesis and applications of trifluoromethyl aryldiazirine photophore
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Date
23/11/2011Author
Valles-Miret, Mariona
Metadata
Abstract
Photoreactive groups have been used in photoaffinity labelling of chemical
macromolecules via the generation of highly reactive species upon short wave light
irradiation. One of the most efficient photoreactive functional groups is
trifluoromethyl aryldiazirine (TFMAD). This compound was synthesised as part of
the work discussed in this thesis, making use of microwave irradiation to shorten
reaction times (Chapter I). An investigation of properties allowed the development
of three different applications for conjugation to biomolecules. The first application
consisted of the development of an approach for generation of small-molecule
microarrays, where a 2,000 compound library was immobilised onto the glass
surface through carbene insertion. The microarray was then used to screen for
potential binders to beta-transducin repeat containing protein (b-TrCP1) allowing
the reduction of possible candidates to less than 25 compounds (Chapter II). The
second application was the synthesis of two probes to allow the selective delivery of
active compounds inside specific organelles or cells. The diazirine moiety was used
as a rapid way to covalently capture a number of cargos. The approach allowed a
peptoid and an anticancer drug to be conjugated to the two probes and their cell
penetrability properties and therapeutic effect were studied, respectively (Chapter
III). Finally, the insertion properties of TFMAD were used to develop approaches to
attach DNA onto microspheres and the efficiency of this delivery system was
evaluated (Chapter IV).