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, a nd catalysts, for use in pharmaceutics, personal care, functional foods, cr op protection, laboratories, offices, and industrial processes, require sta bilization against oxidation and degradation or shielding from sensitive en vironments. Therefore, binding them to carriers with high affinity and sele ctivity for targeting to the right environment and subsequent controlled re lease is beneficial, especially if this allows improved control of (stimulu s-induced) release. Proteins often possess one or more of these properties, whereas modern biotechnology and bioinformatics provide an increasing numb er of tools to engineer and adapt these properties. Carrier systems are now developed that incorporate proteins as the central ligand-binding componen t, e.g., lectins for glucose-triggered release of glycosylated insulin and bispecific antibodies for brain targeting of drugs, but ligand-binding prot eins 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 periplasmi c proteins, lectins, serum albumins, immunoglobulins, and inactivated enzym es. Disadvantages, such as enzymatic degradation or immunogenicity, associa ted with the pharmaceutical use of certain proteins can be avoided by incor porating these proteins in more complex carrier and targeting systems. In o ther applications, this may not be necessary. The enclosure of high-affinit y (potentially stimulus-sensitive) binding proteins within an envelope that acts as a diffusion barrier for the ligand may provide excellent slow rele ase. Many possibilities seem to be as yet unexplored.