biostudies-literatureCabalteja CCDivision of ChemistryNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHS987-997https://www.ebi.ac.uk/biostudies/studies/S-EPMC9039985biostudies-literatureUnknown17(4)The emergence of resistance to clinically used antibiotics by bacteria presents a significant problem in public health. Natural antimicrobial peptides (AMPs) are a valuable source of antibiotics that act by a mechanism less prone to the evolutionary development of resistance. In an effort to realize the promise of AMPs while overcoming limitations such as poor biostability, researchers have sought sequence-defined oligomers with artificial amide-based backbones that show membrane-disrupting functions similar to natural agents. Most of this precedent has focused on short peptidomimetic analogues of unstructured chains or secondary folds; however, the natural antimicrobial arsenal includes a number of small- and medium-sized proteins that act via an ordered tertiary structure. Generating proACS chemical biologyHeterogeneous-Backbone Proteomimetic Analogues of Lasiocepsin, a Disulfide-Rich Antimicrobial Peptide with a Compact Tertiary Fold.PMC9039985CHE 1625002AI133351GM107161R01 GM107161R01 AI133351Lin QHarmon TWCabalteja CCHorne WSRao SRDi YPfalseHeterogeneous-Backbone Proteomimetic Analogues of Lasiocepsin, a Disulfide-Rich Antimicrobial Peptide with a Compact Tertiary Fold.The emergence of resistance to clinically used antibiotics by bacteria presents a significant problem in public health. Natural antimicrobial peptides (AMPs) are a valuable source of antibiotics that act by a mechanism less prone to the evolutionary development of resistance. In an effort to realize the promise of AMPs while overcoming limitations such as poor biostability, researchers have sought sequence-defined oligomers with artificial amide-based backbones that show membrane-disrupting functions similar to natural agents. Most of this precedent has focused on short peptidomimetic analogues of unstructured chains or secondary folds; however, the natural antimicrobial arsenal includes a number of small- and medium-sized proteins that act via an ordered tertiary structure. Generating pro2022-01-01T00:00:00Z2022 Apr2026-05-09T22:22:45.421Z2025-02-19T04:46:16.535ZS-EPMC90399853529001910.1021/acschembio.2c00138