An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity

Bolt, H.L.; Denny, P.W.; Cobb, S.L.

Abstract

This protocol describes the manual solid-phase synthesis of linear peptoids that contain two differently functionalized cationic monomers. In this procedure amino functionalized 'lysine' and guanido functionalized 'arginine' peptoid monomers can be included within the same peptoid sequence. This procedure uses on-resin (N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) or Dde protection, orthogonal conditions to the Boc protection of lysine monomers. Subsequent deprotection allows an efficient on-resin guanidinylation reaction to form the arginine residues. The procedure is compatible with the commonly used submonomer method of peptoid synthesis, allowing simple peptoids to be made using common laboratory equipment and commercially available reagents. The representative synthesis, purification and characterization of two mixed peptoids is described. The evaluation of these compounds as potential anti-infectives in screening assays against Leishmania mexicana is also described. The protozoan parasite L. mexicana is a causative agent of cutaneous leishmaniasis, a neglected tropical disease that affects up to 12 million people worldwide.

Citation

Bolt, H., Denny, P., & Cobb, S. (2016). An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity. Journal of Visualized Experiments, 117, Article e54750. https://doi.org/10.3791/54750

• Journal Article Type: Article
• Acceptance Date: May 13, 2016
• Online Publication Date: Nov 2, 2016
• Publication Date: Nov 2, 2016
• Deposit Date: Oct 13, 2016
• Publicly Available Date: Dec 14, 2016
• Journal: Journal of Visualized Experiments
• Electronic ISSN: 1940-087X
• Publisher: MyJove Corporation
• Peer Reviewed: Peer Reviewed
• Volume: 117
• Article Number: e54750
• DOI: https://doi.org/10.3791/54750
• Public URL: https://durham-repository.worktribe.com/output/1374596