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Updated: Jun 25, 2026

Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
Published on: January 26, 2016
Structure-based design and synthesis of macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors
Rainer Machauer1, Siem Veenstra, Jean-Michel Rondeau
1Novartis Institutes for BioMedical Research, Novartis Pharma AG, PO Box, CH-4002 Basel, Switzerland.
Abstract:
The hydroxyethylene octapeptide inhibitor OM99-2 served as starting point to create the tripeptide inhibitor 1 and its analogues 2a and b. An X-ray co-crystal structure of 1 with BACE-1 allowed the design and syntheses of a series of macrocyclic analogues 3a-h covalently linking the P1 and P3 side-chains. These inhibitors show improved enzymatic potency over their open-chain analogue. Inhibitor 3h also shows activity in a cellular system.

