Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/77124
Title: Optimizing the synthesis of teixobactin and investigating the effects of cationicity of the macrocyclic pharmocophore on antibacterial activity
Authors: Ng, Belle Min Yee
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2019
Abstract: Following the widespread use and abuse of antibiotics, bacteria have evolved a diverse array of strategies to evade elimination by these antimicrobial drugs, a phenomenon commonly known as antibiotic resistance. The capacity for bacteria to develop resistance against multiple types of antibiotics poses a serious threat to public health. Teixobactin, an antimicrobial peptide discovered in 2015, has displayed promising potential as a novel antibiotic given its bactericidal action and apparent insusceptibility to resistance development. In the present study, four teixobactin analogues were synthesized by solid-phase peptide synthesis following a unique scheme that allows for on-resin esterification and macrolactamization to form the cyclic depsipeptide core of teixobactin. This was achieved by using the thiol of cysteine, which substituted one of the residues within the macrocyclic ring, as an anchoring point to the resin. The cysteine residue could be desulfurized to alanine or modified by an alkylating agent to afford different analogues. We investigated the effect of cationicity at position 10 on the structure-activity relationship of teixobactin and showed that the presence of positive charge at position 10 was not required for the antimicrobial activity of the peptide.
URI: http://hdl.handle.net/10356/77124
Rights: Nanyang Technological University
Fulltext Permission: restricted
Fulltext Availability: With Fulltext
Appears in Collections:SBS Student Reports (FYP/IA/PA/PI)

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