VSG as unexpected drug target for sleeping sickness
Prof. Dr. Markus Engstler
Cell and Developmental Biology
At any given time African trypanosomes express just one out of several hundred variant surface glycoprotein (VSG) genes. The sporadic switch in VSG expression forms the molecular basis of antigenic variation. We have found that certain triphenylmethanes (TPMs) bind to all VSG variants tested. In the presence of light, some TPMs become highly toxic for the parasites. We plan to decipher the molecular mechanism of TPM-toxicity and want to exploit those findings for rational design of TPM-based trypanocidal compounds.
Selected, SFB-relevant Publications
G. Hiltensperger, N. G. Jones, S. Niedermeier, A. Stich, M. Kaiser, J. Jung, S. Puhl, A. Damme, H. Braunschweig, L. Meinel, M. Engstler, U. Holzgrabe; Synthesis and structure-activity relationships of new quinolone-type molecules against Trypanosoma brucei. J Med Chem 2012, 55, 2538-2548.