Enhancing the Potency of the Antimalarial Agent, WEHI-601, Through Stereoselective Fluorination
Ishika Jaitly1, Nathan Carey1, Jonathan Li1
1School of Chemistry, University of New South Wales (UNSW), Sydney, Australia.
Abstract:
WEHI-601 is a statine-containing peptidomimetic that inhibits the malarial aspartyl protease, plasmepsin V. In this work, stereoselective fluorination is investigated as a strategy for enhancing the potency of WEHI-601 through conformational bias. Consistent with prediction, a fluorostatine-containing analogue of WEHI-601 is found to deliver stronger antimalarial activity than the lead compound, attributable to conformational preorganisation of the FCCO segment within the peptidomimetic backbone. However, the magnitude of the improvement is small, and this is discussed with reference to the hydrogen bonding capability of the vicinal fluoro-alcohol motif.
Related Concept Videos
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Anthelminthic Agents
ortho–para-Directing Deactivators: Halogens
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase


![Microwave-assisted One-pot Synthesis of N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB)](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F2755.jpg&w=3840&q=50)