title: Delivering Structural Information on the Polar Face of Membrane-Active Peptides:19F-NMR Labels with a Cationic Side Chain.
abstract: Conformationally constrained non-racemizing trifluoromethyl-substituted lysine isosteres [(E)- and (Z)-TCBLys] with charged side chains are presented as a new type of19F-NMR labels for peptide studies. Design of the labels, their synthesis, incorporation into peptides and experimental demonstration of their application for solid state NMR studies of membrane-active peptides are described. A series of fluorine-labeled analogues of the helical amphipathic antimicrobial peptide PGLa(Nle) was obtained, in which different lysine residues in the original peptide sequence were replaced, one at a time, by either (E)- or (Z)-TCBLys. Antimicrobial activities of the synthesized analogues were practically the same as those of the parent peptide. The structural and orientational parameters of the helical PGLa(Nle) peptide in model bilayers, as determined using the novel labels confirmed and refined the previously known structure. (E)- and (Z)-TCBLys, as a set of cationic19F-NMR labels, were shown to deliver structural information about the charged face of amphipathic peptides by solid state19F-NMR, previously inaccessible by this method.
authors.affiliation: Enamine Ltd., vul. Chervonotkatska 78, 02094, Kyiv, Ukraine.
authors.forename: Oleg M
authors.initials: OM
authors.lastname: Michurin
authors.affiliation: Institute of Biological Interfaces (IBG-2), Karlsruhe Institute of Technology (KIT), POB 3640, 76021, Karlsruhe, Germany.
authors.forename: Sergii
authors.initials: S
authors.lastname: Afonin
authors.affiliation: Institute of Organic Chemistry (IOC), KIT, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Berditsch
authors.affiliation: Institute of Organic Chemistry, Westfalische Wilhelms-Universität Münster, Corrensstrasse 40, 48149, Münster, Germany.
authors.forename: Constantin G
authors.initials: CG
authors.lastname: Daniliuc
authors.affiliation: Institute of Biological Interfaces (IBG-2), Karlsruhe Institute of Technology (KIT), POB 3640, 76021, Karlsruhe, Germany.|Institute of Organic Chemistry (IOC), KIT, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.affiliation: Institute of High Technologies, Taras Shevchenko National University of Kyiv, vul. Volodymyrska 60, 01601, Kyiv, Ukraine.
authors.forename: Igor V
authors.identifier: 0000-0002-7908-9145
authors.initials: IV
authors.lastname: Komarov
authors.affiliation: Enamine Ltd., vul. Chervonotkatska 78, 02094, Kyiv, Ukraine.|Institute of Organic Chemistry (IOC), KIT, Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany.
authors.forename: Dmytro S
authors.initials: DS
authors.lastname: Radchenko
keywords: amino acids; fluorine; lysine; peptides; solid state 19F-NMR spectroscopy