OK – maybe that’s hyping it up a bit, but these cyclic peptides are pretty amazing, we think! This is the latest chapter in Karishma’s PhD work (with a massive effort by Biswa Mohanty too!):
In the manuscript, we describe mRNA-display-derived cyclic peptides that bind two copies of a BET-family bromodomain in a highly selective manner – and in so doing, form infinite polymers (that, amazingly, Karishma was able to capture as crystal structures). These peptides are by far the most selective BET bromodomain ligands every described. Even more amazingly, it seems that one of these peptides achieves its specificity by sensing differences in the conformational dynamics of its target bromodomain, relative to the corresponding bromodomains from orthologous proteins. It remains to be seen whether this selectivity can be exploited therapeutically – but if it could, it would be very cool…
