S-adenosylmethionine and sinefungin

There is always the possibility that I am only seeing what I want to see, which is in itself slightly unnerving and the reason why I repeatedly ask for feedback from anyone out there. Whether or not anyone who stumbles across these pages is actually involved in science and could potentially use these ideas is another matter. For the time being, all I can do is to write down my thoughts and hope that some day someone will know what to do with them.

I recently came across an old paper on antileishmanial properties of the S-adenosylmethionine-analog sinefungin:

Nolan LL. Molecular target of the antileishmanial action of sinefungin. Antimicrob Agents Chemother. 1987 Oct;31(10):1542-8.

We'll see if and how things may fit together, but sinefungin-mediated inhibition of polyamine synthesis or DNA methylation/ epigenetics might be possible mechanisms worth considering... In fact, sinefungin looks especially cool because it combines being a SAM/SAH-homologue as well as an ornithine derivative...

S-adenosylmethionine

(taken from "http://www.freepatentsonline.com/7048948-0-large.jpg")

Sinefungin

(taken from "http://www.sigmaaldrich.com/thumb/structureimages/59/s______s8559.gif")

Leishmania donovani was shown to be very sensitive to treatment with sinefungin, with even promastigotes being affected by the treatment. Which makes me start to wonder what might have happened to sinefungin in the pipeline to becoming a widely used antileishmanial drug? Is it possible to devise a delivery method for sinefungin which would target macrophages specifically, either by liposomes or linked to peptides that bind to macrophage receptors?

Bachrach U, Schnur LF, El-On J, Greenblatt CL, Pearlman E, Robert-Gero M, Lederer E. Inhibitory activity of sinefungin and SIBA (5'-deoxy-5'-S-isobutylthio-adenosine) on the growth of promastigotes and amastigotes of different species of Leishmania. FEBS Lett. 1980 Dec 1;121(2):287-91.

Phelouzat MA, Basselin M, Lawrence F, Robert-Gero M. Sinefungin shares AdoMet-uptake system to enter Leishmania donovani promastigotes. Biochem J. 1995 Jan 1;305 (Pt 1):133-7.