Mirror image nanobodies: pushing forward the potential of enantiomeric proteins for therapeutic and pharmacological applications. – YDOBONAN

Recent advances in chemical protein synthesis afford unique access to the D-“mirror image” of native L-proteins, enabling protein research to be conducted “through the looking glass”. The most promising, yet rather underexplored, application is the development of “chemical biologics” that would have optimal in vivo properties for medium-sized drugs, such as resistance to proteolysis. This project aims at pushing forward the boundaries of D-protein therapeutics, through three main innovations : (1) the type of scaffolds: single domain antibodies (SDAbs) specific to camelids, optimized by nature to be able to bind any type of antigens; (2) a novel discovery process for D-protein therapeutics, based on in vivo “mirror-image immunization” and (3) the size of the D-proteins (~120 AA). Synthetic protein chemistry is at the heart of the project, complemented with biology and state of the art structural determination by combination of NMR and mirror-image crystallography.