Microwave Assisted SPPS of Unsymmetrically Branched Peptides

Introduction

Unsymmetrically branched peptides can be synthesized via SPPS by using Fmoc-Lys(ivDde)-OH, which contains an orthogonally protected lysine. The ivDde group is stable under conditions necessary for Fmoc removal, but it is facilely cleaved by hydrazinolysis. This allows for the selective generation of an unsymmetrical branch point where a peptide of a different sequence can be coupled at the ε-amine of the lysine sidechain. Unsymmetrical branching has been used to generate peptides with a wide variety of biological functions and chemical properties including compounds with antimicrobial activity, peptides with in vitro deubiquitinase resistance, and macromolecules with antifreeze properties.