Access to Diverse Glutamic Acid Dendrons and a Janus Peptide Dendrimer Using an Atypical Solid Phase Synthesis.

Abstract

The negligible cytotoxicity of anion surface-linked dendrons makes glutamic acid-based dendrons a potential candidate for materials and biological applications. Despite the inherent drawbacks of the conventional solution phase synthesis of glutamic acid-based dendrons, there have been no advancements in these protocols. Herein, we demonstrate the first-ever convergent solid phase synthesis of dendrons, up to fourth generation, having glutamic acid branching points produced by preactivation of dicarboxylic acid groups with N-hydroxysuccinimide and simultaneous coupling with amine groups of two growing peptide chains, with excellent yields (30-70%). In addition to the general advantages, such as the easy workup, a final single purification step, and an overall short synthesis duration, the convergent solid phase synthesis allowed us to chemically synthesize glutamic acid branching-based dendrons that cannot be accessed by standard divergent solid phase synthesis. This method has also been validated for its application in synthesizing hard-to-achieve Janus peptide dendrimers in a single stretch on a solid support. Our work corroborates the efficacy of controlled -COOH activation to accomplish an atypical solid phase synthesis of diverse glutamic acid dendrons in a convergent fashion. This is the first example of a Janus peptide dendrimer being synthesized on a solid support, utilizing both convergent and divergent approaches simultaneously.