Paula M. Dulski

Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 1.

Apicidin, a natural product recently isolated at Merck, inhibits both mammalian and protozoan histone deacetylases (HDACs). The conversion of apicidin, a nanomolar inhibitor of HDACs, into a series of side-chain analogues that display picomolar enzyme affinity is described within this structure-activity study.

The purification of sporocysts and sporozoites from Eimeria tenella oocysts using Percoll density gradients.

A protocol is presented for the purification of sporozoites from sporulated oocysts of Eimeria tenella. Two Percoll density gradients are the basis of the purification. The first gradient is used after glass-bead grinding to purify undamaged sporocysts; 87% of the sporocysts loaded onto the gradient were recovered in the pellet. The second gradient is used after excystation to purify sporozoites; 98% of the sporozoites loaded onto the gradient were recovered in the pellet. The sporozoites are 99% pure with a final recovery of about three sporozoites per oocyst.

A family of glycolipid linked proteins in Eimeria tenella

A number of proteins in Eimeria tenella are shown to possess a carbohydrate similar to that found on the carboxyl terminus of the variant surface glycoprotein from Trypanosoma brucei. In trypanosomes, this carbohydrate is part of a glycolipid structure responsible for membrane attachment. In common with the variant surface glycoprotein and with other glycolipid linked proteins, the E. tenella proteins were shown to be hydrophobic. Treatment with a crude lipase preparation from T. brucei modifies these proteins to a water-soluble form.

N-alkyl-4-piperidinyl-2,3-diarylpyrrole derivatives with heterocyclic substitutions as potent and broad spectrum anticoccidial agents.

Diaryl-(4-piperidinyl)-pyrrole derivatives bearing cyclic amine substituents have been synthesized and evaluated as anticoccidial agents. Improvements in potency of Et-PKG inhibition, such as azetidine derivative 3a, and broad spectrum anticoccidial activities in feed, such as morpholine derivative 8c, have been achieved.