Andrew Derrick Gribble

Solid-phase synthesis of cyclic alkoxyketones, inhibitors of the cysteine protease cathepsin K

Using solid-phase synthesis, a library of novel cyclic alkoxyketones has been constructed which show strong inhibitory activity against the cysteine protease, cathepsin K (EC 3.4.22.38).

Diastereoselective synthesis, activity and chiral stability of cyclic alkoxyketone inhibitors of cathepsin K.

The diastereoselective synthesis of a novel class of cathepsin K inhibitors together with their cathepsin K affinity and stability towards aqueous buffer is reported.

The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives.

Aryl hydroxylamine derivatives have been synthesised that are some of the most potent inhibitors of hCMV protease prepared to date (IC50 14-60 nM). Mass spectrometry studies indicate that oxazinone derived hydroxylamines inhibit the enzyme by acylation of Ser132 whereas non-oxazinone derived hydroxylamines appear to inhibit via formation of a sulfinanilide at Cys138.