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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Biomimetic synthesis of gramicidin s and analogues by enzymatic cyclization of linear precursors on solid support
Xiaoming Wu1, Xianzhang Bu, Ka Man Wong
1Department of Chemistry and Biotechnology Research Institute, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Abstract:
[reaction: see text] Gramicidin S is a potent decapeptide antibiotic with high hemolytic activity but is unlikely to provoke microbial resistance. Here we demonstrate that gramicidin thioesterase (GrsB TE) correctly cyclizes immobilized linear decapeptide precursors into head-to-tail products, indicating its suitability for parallel solid-phase synthesis of gramicidin analogues from linear precursors on solid support. This chemoenzymatic method will enable the optimization of the therapeutic index of the natural product to fight microbial resistance.
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