Ligand-binding proteins: their potential for application in systems for controlled delivery and uptake of ligands

Unstable or harmful agents, such as drugs, vitamins, flavors, pheromones, and catalysts, for use in pharmaceutics, personal care, functional foods, crop protection, laboratories, offices, and industrial processes, require stabilization against oxidation and degradation or shielding from sensitive environments. Therefore, binding them to carriers with high affinity and selectivity for targeting to the right environment and subsequent controlled release is beneficial, especially if this allows improved control of (stimulus-induced) release. Proteins often possess one or more of these properties, whereas modern biotechnology and bioinformatics provide an increasing number of tools to engineer and adapt these properties. Carrier systems are now developed that incorporate proteins as the central ligand-binding component, e.g., lectins for glucose-triggered release of glycosylated insulin and bispecific antibodies for brain targeting of drugs, but ligand-binding proteins can potentially be used in many other applications. Collectively, the proteins available in nature bind an impressive variety of ligands and non-natural analogs. In this light, various ligand-binding protein classes are surveyed, including biotin-, lipid-, immunosuppressant-, insect pheromone-, phosphate-, and sulfate-binding proteins, as well as bacterial periplasmic proteins, lectins, serum albumins, immunoglobulins, and inactivated enzymes. Disadvantages, such as enzymatic degradation or immunogenicity, associated with the pharmaceutical use of certain proteins can be avoided by incorporating these proteins in more complex carrier and targeting systems. In other applications, this may not be necessary. The enclosure of high-affinity (potentially stimulus-sensitive) binding proteins within an envelope that acts as a diffusion barrier for the ligand may provide excellent slow release. Many possibilities seem to be as yet unexplored.