A Novel Scaffold for Liquid Phase Peptide Synthesis

The growing number of peptides approved as drugs is pushing the introduction of synthetic methodologies alternative to the solid‐phase peptide synthesis (SPPS), currently the most exploited method for large‐scale peptide production. Indeed, SPPS is easily scalable, can be automated, and allows the synthesis of long peptides in short times. However, it also has some disadvantages, as it uses large excesses of reagents, huge amounts of solvents (often not “green"), a non‐biodegradable solid support, and features a heterogeneous reaction environment in which amino acid couplings are more difficult than in a homogeneous environment. For this reason, in recent years there has been growing interest in developing better synthetic methods. In this work, we present a new dendrimeric support based on lysine (Lys) and short polyethylene glycol (PEG) chains. Its main advantages are (i) the possibility of using more eco‐friendly solvents that cannot be used in standard SPPS, (ii) the replacement of polystyrene‐based supports with a PEG‐lysine hybrid one, and (iii) the formation of a homogeneous reaction medium that will help to reduce the excess of reagents and solvents. The results obtained in the synthesis of a model peptide are promising and amenable to transfer to an industrial scale.