Proteolytic resistant peptidomimetics for therapeutic development

Peptoid Synthesis Method

The synthesis of a peptoid can be achieved through two methods: monomer and submonomer.

Monomer method: This method is very similar to solid phase synthesis of peptide with the exception that all the protected monomers for peptoid synthesis need to be synthesized first, where the synthesis of every Nα-protected monomer is tedious and time-consuming.

Fig.2 Synthesis of peptoid monomers

Submonomer method: This method eliminates the need of Nα-protected monomers. Each residue is installed in two steps: acylation followed by nucleophilic displacement. The submonomer approach allows the use of any commercially available or synthetically accessible amine that has great potential for combinatorial chemistry. In the acylation step a haloacetic acid, typically bromoacetic acid, is activated by diisopropylcarbodiimide reacting with the amine of the previous residue. In the displacement step (a classical SN2 reaction), an amine displaces the bromide to form an N-substituted glycine residue. This approach has greater advantages over the monomer approach and has been widely applied to peptoid library construction. We currently apply the Submonomer method for peptoid synthesis.

Fig.3 Schematics of peptoid synthesis by submonomer method

Case Study

With proven technical capability and state-of-the-art in-house instruments and technologies, we have successfully synthesized many peptoids.

Sequence: Npip-NVal-Npa-NIle-NLeu-Nnba-Nmba-Ndmb-Nmpe-NIle-Npea-Ndmb-NPhe-NVal-NAla-Nea-NLeu-NAla-NPhe-Nnba-Npa

Structure:

Length: 21 residues

Purity: 98.3%

Theoretical MW: 2733.37

Observed MW: 2732.8

MS result checked by ESI:

HPLC result checkedy by RP-HPLC, C18 column: