Abstract

The development of new chemical tools and strategies are indispensable to the study of complex biological problems. Cellular processes are driven by the functions of its proteins. The ability of a single protein to modulate a number of different functions, in a highly regulated manner, relies on its ability to be posttranslationally modified in response to various stimuli. The development of tools that enable the investigation of the dynamics and regulation of protein function would help answer fundamental questions in signal transduction and disease pathology. In this work novel protein domains have been developed that are switchable by phosphorylation from a non-fluorescent to fluorescent state. Composed entirely of encodable amino acids, these domains will enable the fluorescent read-out of kinase activity in endogenous systems.

Libraries of complex molecules with functional group diversity can be constructed in a modular fashion from simple building blocks. The development of such building blocks comprising privileged functionalities such as chiral guanidiniums will enable the targeting of a wide range of macromolecules in a rapid manner. The synthesis and scope of chiral α-guanidino acids have been described. The application of α-guanidino acids as arginine mimics in the development of novel Src homology 3 (SH3) ligands have also been described.