Functional protein scaffolds

Lars Baltzer’s research group has developed a new and unprecedented concept for protein recognition and binding, where small organic molecules are covalently linked to 42-residue polypeptides (Fig. 1) to form binders with affinities and selectivities equal to, or better, than those of mAbs, in spite of being only 1/30 the size of an IgY.

Fig. 1. General illustration of the binder concept.

The polypeptides enhance the affinities for proteins of small molecules by 3 - 4 orders of magnitude and offer a rapid route to high-affinity recognition of protein targets. The binders are robust and do not denature, even upon boiling. They do not depend on a preorganized fold and structure for their function, but follow an induced fit mechanism, and are therefore suitable for use under demanding conditions. These synthetic binders are readily functionalized with e. g. gold nanoparticles, fluorophores (Fig. 2), radionuclides etc., and have turned out to be of great interest in clinical diagnostics, in molecular imaging, in drug development and as potential drugs.

Within the UMC project, the goal is to incorporate a panel of binders into multiplex chips, to be used in the field for detection of specific microbial enzymes in soil and water samples.