Biomedical subjects
Publications and source records attributed to Michael M Meijler.
Constrained nicotine analogues were synthesized and coupled to the carrier protein KLH. The immunogenic effects were compared to those using our previously designed flexible nicotine hapten. Immunization of mice with the constrained hapten conjugates resulted in highly increased antibody titers and affinity for nicotine.
Synthetic iron chelators based on the natural siderophore ferrichrome have previously been shown to bind Fe(III) with high affinity (pKf > 27) and have shown no toxicity to mammalian cell cultures in vitro. A new class of lipophilic ferrichrome analogues carrying acetoxymethyl ester moieties has been synthesized. We have shown that these molecules penetrate rapidly through cell membranes and turn highly hydrophilic while inside the cells, upon esterase mediated hydrolysis of the lipophilic termini. The intracellular retention was visualized by labeling these analogues with a fluorescent naphthalic diimide probe. The prohydrophilic iron chelators have been shown to inhibit the metal-catalyzed intracellular formation of reactive oxygen species with high effectivity, and preliminary results suggest these molecules to be potent antimalarial agents.