title: Bacterial display and screening of posttranslationally thioether-stabilized peptides.
abstract: A major hurdle in the application of therapeutic peptides is their rapid degradation by peptidases. Thioether bridges effectively protect therapeutic peptides against breakdown, thereby strongly increasing bioavailability, enabling oral and pulmonary delivery and potentially significantly optimizing the receptor interaction of selected variants. To efficiently select optimal variants, a library of DNA-coupled thioether-bridged peptides is highly desirable. Here, we present a unique cell surface display system of thioether-bridged peptides and successfully demonstrate highly selective screening. Peptides are posttranslationally modified by thioether bridge-installing enzymes in Lactococcus lactis, followed by export and sortase-mediated covalent coupling to the lactococcal cell wall. This allows the combinatorial optimization and selection of medically and economically highly important therapeutic peptides with strongly enhanced therapeutic potential.
authors.affiliation: LanthioPep, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Tjibbe
authors.initials: T
authors.lastname: Bosma
authors.forename: Anneke
authors.initials: A
authors.lastname: Kuipers
authors.forename: Erna
authors.initials: E
authors.lastname: Bulten
authors.forename: Louwe
authors.initials: L
authors.lastname: de Vries
authors.forename: Rick
authors.initials: R
authors.lastname: Rink
authors.forename: Gert N
authors.initials: GN
authors.lastname: Moll
mesh_terms: D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism*; D013294:Lactococcus lactis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008403:Mass Screening / Q000379:methods*; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D021381:Protein Transport; D013440:Sulfides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010455:Peptides; D013440:Sulfides