Strategies to Identify the Target of Praziquantel

Published by MatTodd on 22 October 2007 - 9:57pm

There are three obvious methods to identify PZQ's in vivo target: 1) Radiolabelled PZQ (tritiated probably best). It's likely that the interaction between PZQ and its target is not long-lived, which means purely radiolabelled PZQ is not the best strategy. 2) Solid-supported PZQ. It may be possible to attach PZQ to a solid support and pass the parasite proteome down a column of this support to identify retarded proteins. For preliminary results in this direction see the actin project page. 3) A strong approach is the attachment of a photoaffinity probe to PZQ, e.g. an azide. Incubation of photoaffinity-PZQ ("hv-PZQ") with schistosome extract followed by irradiation with UV light should cross-link the PZQ with the target protein. Naturally such proteins need to be identified, implying a radioactive photoaffinity probe is needed, which is more difficult and expensive to make. For approaches 2 and 3, a suitable place to attach things to PZQ must be found, which links to the search for effective analogs of PZQ where variation in the structure of the molecule is tolerated.