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The impact of backbone N ‐methylation on the structure‐activity relationship of Leu 10 ‐teixobactin
Author(s) -
Velkov Tony,
Swarbrick James D.,
Hussein Maytham H.,
SchneiderFutschik Elena K.,
Hoyer Daniel,
Li Jian,
Karas John A.
Publication year - 2019
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3206
Subject(s) - antimicrobial , chemistry , natural product , peptide , combinatorial chemistry , structure–activity relationship , methylation , biological activity , stereochemistry , biochemistry , computational biology , biology , gene , in vitro , organic chemistry
Antimicrobial resistance is a serious threat to global human health; therefore, new anti‐infective therapeutics are required. The cyclic depsi ‐peptide teixobactin exhibits potent antimicrobial activity against several Gram‐positive pathogens. To study the natural product's mechanism of action and improve its pharmacological properties, efficient chemical methods for preparing teixobactin analogues are required to expedite structure‐activity relationship studies. Described herein is a synthetic route that enables rapid access to analogues. Furthermore, our new N ‐methylated analogues highlight that hydrogen bonding along the N ‐terminal tail is likely to be important for antimicrobial activity.