Photoremovable protecting groups are important for a wide range of applications in peptide chemistry.  For thiol protection, the most widely used approach involves masking with an o-nitrobenzyl group.  In earlier work, we demonstrated that the brominated hydroxycoumarin (Bhc) group could be used for thiol group protection in peptidomimetic enzyme inhibitors.  The two-photon excitation properties allowed that group to be efficiently removed for biological applications in cell culture.  However, interestingly, the use of the Bhc group in peptides is complicated by the formation of an isomeric product that occurs in the photolysis reaction.  We have recently characterized that compound.  To circumvent that problem, we have prepared cysteine-containing peptides where the thiol is protected with a nitrodibenzofuran (Ndbf) group.  That was accomplished by preparing Fmoc-Cys(Ndbf)-OH and incorporating the residue into peptides by standard solid phase peptide synthesis.  Irradiation with 360 nm light gave clean conversion to the free thiol.  Deprotection was also obtained via two-photon excitation with 800 nm light.  Thiol group uncaging was carried out on peptides that are substrates for protein farnesyltransferase in the presence of the enzyme resulting in the formation of prenylated products.  Those experiments indicate that deprotection can be performed under mild conditions that allow enzymatic activity to be retained suggesting that the Ndbf group should be useful for caging thiol groups in peptides used for biological experiments.

Nitrodibenzofuran: A new photoremovable group for thiol protection in peptides

247th National Meeting (2014)

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