Just Build The Thing

Here's a paper that's just come out in JACS that's worth a look on more than one level. It describes a way to image prostate cancers in vivo by targeting the GPR receptors on the cell surfaces, which are overexpressed in these tumors. Now, this is already done, using radiolabeled bombesin peptides as ligands, but this new work brings a new dimension to the idea. What the authors have done is targeted the cell surface with antagonists and agonists at the same time, by hooking these onto a defined molecular framework. That's poly-proline, which is both soluble and adopts a well-defined structure once it's in solution. The bombesin derivatives are attached via a click Huisgen triazole linkage, and since you can slot in an azidoproline wherever you want, this lets you vary the distance between the two peptides up and down the scale. The hope is that having both kinds of ligand going at the same time might combine their separate advantages (binding potency and uptake into the cells). And that idea seems to work: one of the combinations (the one with about a 20A spacing between the two ligands) works noticeably better than either radiolabeled peptide alone, with greater uptake and longer half-life. I'd say that proof of concept has been achieved, and the authors are planning to extend the idea to other known cell-surface-binding oncology ligands used diagnostically and/or therapeutically. Each of these will have to be worked out empirically, since there's no way of knowing what s...
Source: In the Pipeline - Category: Chemists Tags: Cancer Source Type: blogs