4503

Synthesis of Cyclic Peptidomimetic and their Prodrugs

Gilon Chaim, HUJI, Faculty of Science, The Institute of Chemistry
Hoffman Amnon, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

Keywords

Platform technology, Intestinal permeability, Lipophilic Prodrug Charge Masking, peptides, oral bioavailability

Current development stage

TRL4 - POC & Safety of candidate drug formulation is demonstrated in defined animal model

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 

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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

 

Contact for more information:

Ariela Markel
VP, Business Development, Healthcare
+972-2-6586608
Contact ME:
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