276: Synthesis of di-𝘕-carboxyanhydride cross-linkers for preparation of synthetic polypeptides

Synthesis of di-N-carboxyanhydride cross-linkers for preparation of synthetic polypeptides

Veronika Syrová, Ema Žagar, and David Pahovnik^*

Department of Polymer Chemistry and Technology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia; e-mail: veronika.syrova@ki.si

The introduction of cross-links into polymer chains influences the physical properties of the polymer material. The extent of this effect depends on the degree of polymer cross-linking. This tunability allows for the creation of polypeptides with a wide range of stiffness and elasticity. To prepare cross-linked synthetic peptides by ring-opening polymerization of N-carboxyanhydride (NCA) monomers, a suitable di-N-carboxyanhydride (di-NCA) cross-linker must be used, the reactivity of which should match that of the monomer(s). 

Since α-amino acid derivatives based on glutamic acid and lysine are most commonly used for the preparation of synthetic polypeptides, we investigate the preparation of asymmetric and symmetric di-NCA cross-linkers based on glutamyl-lysine (Glu-Lys) isopeptide, lysyle-lysine (Lys-Lys) dipeptide and glutamyl-glutamic acid dipeptide (Figure 1). The Leuch method of NCA synthesis using different halogenating agents proved to be suitable for the preparation of both asymmetric and symmetric di-NCAs. In order to maintain the stability of the symmetric crosslinkers, the amide bond between an amino acid and various linkers have to be preserved.