The function of many cancer related proteins is modulated by modifications such as phosphorylation and glycosylation. The development of antibodies that recognize site-specific phosphorylation has vastly improved our understanding of signal transduction and cancer cell physiology and regulation. However, almost no available antibodies recognize site specific glycosylation, and in particular, N-acetylglycosamine modification of serines and threonines (O-GlcNAc). Possible reasons for this are poor immunogenicity in animals, or that antibodies are not appropriate for recognizing OGlcNAc in a site specific fashion. These limitations may make it extremely challenging to generate site-specific anti-OGlcNAc antibodies with sufficient affinity and selectivity to be useful research tools. A non-antibody-based approach has the potential to serve as an alternative method for generating affinity capture reagents that recognize site-specific OGlcNAc. Aptakon has developed a 14 kD protein scaffold with randomizable binding loops that is not subject to the limitations described for antibodies. Aptakon aims to: screen phagemid libraries of this scaffold for binders to O-GlcNAc modified regions of cancer relevant proteins;generate applications data for these binders;optimize a master library for identifying O-GlcNAc modified peptides;and to produce standard operational procedures for isolation and characterization of these high affinity binders. This technology has the potential to spawn significant advances in cancer related signal transduction research similar to the advent of phospho-specific antibodies. These new products will have the potential to increase the productivity of researchers and thereby accelerate the development of drugs and diagnostic tests for cancer.
