title: PEGylated substrates of NSP4 protease: A tool to study protease specificity.
abstract: Herein we present the synthesis of a novel type of peptidomimetics composed of repeating diaminopropionic acid residues modified with structurally diverse heterobifunctional polyethylene glycol chains (abbreviated as DAPEG). Based on the developed compounds, a library of fluorogenic substrates was synthesized. Further library deconvolution towards human neutrophil serine protease 4 (NSP4) yielded highly sensitive and selective internally quenched peptidomimetic substrates. In silico analysis of the obtained peptidomimetics revealed the presence of an interaction network with distant subsites located on the enzyme surface.
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wysocka
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gruba
authors.affiliation: Faculty of Chemistry, Wroclaw Technical University, Wroclaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Grzywa
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Giełdoń
authors.affiliation: Faculty of Chemistry, University of Wroclaw, Wroclaw, Poland.
authors.forename: Remigiusz
authors.initials: R
authors.lastname: Bąchor
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Brzozowski
authors.affiliation: Faculty of Chemistry, Wroclaw Technical University, Wroclaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Sieńczyk
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Jenne
authors.initials: J
authors.lastname: Dieter
authors.affiliation: Faculty of Chemistry, University of Wroclaw, Wroclaw, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Szewczuk
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Rolka
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Lesner
mesh_terms: D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D053146:Myeloblastin / Q000378:metabolism*; D057786:Peptidomimetics / Q000737:chemistry / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity
chemical_list: D005456:Fluorescent Dyes; D057786:Peptidomimetics; D053146:Myeloblastin