Poster Presentation 13th Australian Peptide Conference 2019

Cyclic peptides have emerged as valuable pharmaceutical templates due to their resistance to chemical or enzymatic hydrolysis and high selectivity. In 2001, the celogentin family of bicyclic peptides was isolated from the seeds of Celosia argentea. The celogentins have been shown to be t potent anti-mitotic agents that inhibit tubulin polymerization, with celogentin C exhibiting four-fold higher activity than the clinically used anti-cancer drug vinblastine.^1,2 The celogentins have two unusual side-chain to side-chain cross-links; one between the β-position of Leu2 and the indole C-6 of Trp5 and the other between the indole C-2 of Trp5 and the imidazole of the histidine side chain. These unusual cross-links make the chemical synthesis of the celogentins very tedious, lengthy, and low yielding. We have developed a new protocol for the formation of the C–C and C–N cross-links on solid phase to generate celogentin precursors. We have also designed and synthesized simplified celogentin mimetics, including analogues with improved biological activity.³ 

Reference:

1. Feng, Y.; Chen, G., Chem. In.t Ed. 2010, 49, 958-61.
2. Ma, B.; Banerjee, B.; Litvinov, D. N.; He, L.; Castle, S. L., Am. Chem. Soc., 2010, 132, 1159-1171.
3. Thombare, V. J.; Holden, J. A.; Pal, S.; Reynolds, E. C.; Chattopadhyay, A.; O'Brien-Simpson, N. M.; Hutton, C. A., Tetrahedron 2018, 74, 1288-1293.