Cyclic peptide synthesis and production methods to create cyanobactin, divimides, and other cyclic peptide libraries for use in drug design, discovery, and therapeutics.

Cyclic peptide libraries of novel compounds serve as valuable collections for researchers to mine for new therapeutics. The proposed methods for creating cyclic peptide libraries utilize biosynthetic pathways from various organisms. The enzymatic steps are broken into individual components and then reassembled in unique was to generate large collections of novel chemical entities (NCEs).

One method uses amide-linked peptides created in vivo by expression of constructs in E. coli. Another method centers on prenylated compounds created from marine ascidian enzymes, again expressed in E. coli. The final method utilizes natural pathways from sponges to synthesize compounds for libraries. Methods to increase the yield and potency of peptides, specifically cyanobactin and prenylated peptides, in the libraries have also been developed.

Design & Development

• Facilitates production of cyclic peptides libraries with unique novel chemical entities.
• Enables in vivo and in vitro production.
• Demonstrates potential for anticancer, antifungal, drug discovery, drug design, and drug screening applications.
• Expands scope to include proteins and non-peptide materials.

Zhang S, et al. (2017). Identification of cyclic depsipeptides and their dedicated synthetase from Hapsidospora irregularis. Journal of Natural Products. 80(2):363-370. doi: 10.1021/acs.jnatprod.6b00808

Otaka A, et al. (2017). Cysteine-Free intramolecular ligation of N-Sulfanylethylanilide peptide using 4-Mercaptobenzylphosphonic Acid: Synthesis of cyclic peptide trichamide. Synlett. 28(15):1944-1949. doi: 10.1055/s-0036-1589055

Publication Number: 1998792
Patent Title: Methods and Compositions Related to Cyclic Peptide Synthesis
Jurisdiction/Country: European Patent Office (EPO)
Application Type: Non-Provisional

Jason Young
(801) 587-0519
jason.r.young@utah.edu