Platform Technology for Synthesis of Cyclic Peptidomimetics and their Prodrugs

Application

• Peptides are key players in a variety of physiological and pathological processes and play very important roles in modulating various cell functions.
• One of the most important challenges developing peptide drugs is the lack of appropriate physicochemical properties that enables the absorption through biological membranes.
• Currently, most peptide drugs are administered parentally due to their poor intestinal permeability attributed to their  hydrophilicity mainly due to charged groups.

Our Innovation

• A novel method called Lipophilic Prodrug Charge Masking (LPCM) that enhance the intestinal permeability and the oral bioavailability of charged peptides
• Significantly increased permeability rate of most peptides compared to the respective unmasked peptides.
• Brings into the systemic blood circulation the parent drug.
• Converts active peptides to orally therapeutic treatment

Technology

• The major challenges in peptide membrane permeability via passive diffusion include the peptide’s high polarity, charge and hydrogen bond potential.
• In the LPCM method, synthetic methods for the conversion of peptides, peptidomimetic and peptide drugs into their lipophilic prodrug were demonstrated.
• Charged masked peptide prodrugs were synthesized and masked with urethane/ ester type lipophilic pro-moiety.  The prodrug enhanced intestinal permeability allowed its absorption to the blood stream where esterases removed the pro-moiety to regenerate the original peptides.
• The LPCM method shifts the mechanism of intestinal permeability of the charged peptides from para-cellular to trans-cellular pathway of their lipophilic prodrug 

Fig. 1: Principle of the LPCM method

Opportunity

• New oral peptides/peptidomimetics medications
• Chronic treatment with good patient compliance
• Currently being studied  and tested for RGD containing peptide

Patent Status

Published WO 2019/058367 A1; WO 2019/058374