Local delivery of proteins and the use of self-assembling peptides
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Drug discovery today. - London
, p. 561-568
Self-assembling peptides are members of a new class of molecules designed for tissue engineering and protein delivery. Upon injection in a physiological environment, self-assembling peptides form stable nanofiber hydrogels. Such biocompatible nanofibers can support three-dimensional growth and differentiation of many cell types. Self-assembling peptides are promising candidates for protein delivery, because they allow non-covalent binding of proteins, tethering of proteins, or incorporation of fusion proteins. Self-assembling peptides can be designed to deliver individual proteins or multiple factors, because the building blocks comprising self-assembling peptides can be designed with great flexibility. Until relatively recently, a significant proportion of the strategies for treating diseases involved the use of the time-honored approach of antagonism of receptors by small molecule drugs. However, the small molecule antagonism approach is unsuitable for a broad variety of biological processes. For example, activation rather than inhibition of the system may be desirable and this can be difficult using typical drug design strategies. In addition, small molecules are often incapable of generating the effect that a protein can, since the protein often acts over a much larger polar surface area (a typical proteinprotein interface covers ∼1600 Å2 of protein surface area ). Proteins and peptides, natural or engineered, are often excellent candidates for therapeutic agents as millions of years of evolution has represented a far superior SAR campaign, with respect to specificity and potency, than can be achieved in the laboratory. Thus, it is not surprising that biological therapies, in particular antibodies and engineered proteins, are comprising an ever-increasing proportion of approved therapies . A logical next step will be to produce biomedical therapies that are a combination of small molecules, proteins, and even cells, which may allow more flexibility in the design of future therapies.