Disruptor Therapeutics

Interacting peptides identified by peptide array analyses also have the potential to be used to develop therapeutic agents to disrupt protein-protein interactions. It has become evident that targeting and compartmentalization are fundamental to the functioning of PDE4s, such that disrupting protein-protein interactions with competing peptides can be predicted to abolish specific functioning of an isoform. Peptides themselves do not make good pharmacological agents due to problems of delivery, poor bioavailability and metabolic instability. However, interacting pep-tides can be used as a basis to design small molecule peptidomimetics that retain the ability to bind to the biological target, but that avoid the problems associated with natural peptides (Adessi and Soto 2002). These small molecule therapeutics will not be without their problems; for example, peptide-based drugs might be expected to be less soluble than existing PDE4 inhibitors. Additionally, the disruption of pre-existing protein-protein interactions may be problematic if their affinity is high, although in chronic disease states, continuous treatment with a small molecule disruptor could block the site of interaction on nascent proteins before they have the chance to form any high-affinity interactions. Despite these anticipated problems, this new class of PDE4 inhibitors would have the advantage of being highly specific, which would hopefully eliminate the side effects associated with current inhibitors and so be of great benefit in the treatment inflammatory disease, auto-immune disease and depression.

0 0

Post a comment