Synthetische Analoga zeigen die essentiellen Strukturmotive von Lugdunin und seinen Protonentransport

Abstract

Lugdunin, ein neues Thiazolidin-Cyclopeptid, weist gegenüber Methicillin-resistentem Staphylococcus aureus (MRSA) antimikrobielle Wirkung im mikromolaren Bereich auf.Fürdie Untersuchung von Struktur-Aktivitätsbeziehungen (SAR) wurden synthetische Alanin-und Stereo-Derivate sowie Peptide mit modifiziertem Thiazolidinring auf ihre antimikrobielle Aktivitätg etestet. Sowohl das Thiazolidin als auch die d-, l-alternierende Konfiguration stellen essentielle Strukturmotive dar.B emerkenswert ist die identischeA ktivitätd es Enantiomers,w as eine stereospezifische Wechselwirkung mit einem Zielmoleküla usschließt. Die antibakterielle Wirkung korreliert stark mit dem Einbrechen des Membranpotentials von S. aureus.Lugdunin gleichtpH-Gradienten in künstlichen Membranvesikeln unter Erhalt der Membranintegritäta us. Der Wirkmechanismus (MoA) beruht somit auf Protonentransport. Der Einbau eines zusätzlichen Tryptophans oder einer Propargylfunktion erweitert die Diversitätd ieser neuen Substanzklasse der Thiazolidin-Cyclopeptide.

CyClick Chemistry for the Synthesis of Cyclic Peptides

“…Cyclic peptides have recently received considerable attention in the pharmaceutical industry because of their high stability, cell permeability, and enhanced potency as compared to their linear counterparts . Currently, more than 40 cyclic peptides are used as pharmaceuticals, and most of them are obtained from nature . The major driving force for the growing interest in cyclic peptides is due to their ability to interrupt protein–protein interactions (PPIs) in a highly specific manner .…”

“…[1][2][3][4][5] Currently,m ore than 40 cyclic peptides are used as pharmaceuticals,and most of them are obtained from nature. [6][7][8] Themajor driving force for the growing interest in cyclic peptides is due to their ability to interrupt protein-protein interactions (PPIs) in ah ighly specific manner. [9][10][11] Despite their importance,l aboratory synthesis of cyclic peptides can be challenging.A mong the most challenging cyclizations are those attempted on linear peptides containing less than seven amino acid residues.…”

Total synthesis, structure elucidation and expanded bioactivity of icosalide A: effect of lipophilicity and ester to amide substitution on its bioactivity

“…[1][2][3][4] A repertoire of antibiotic molecules that act by distinct mechanisms and are not extensively used would help tackle infectious diseases more effectively in times of pandemics or widely spreading infections. [5][6][7] Hence, searching for newer antibiotic substances belonging to different structural classes that act efficiently and by novel mechanisms of action is a continuous process. 8,9 Among the various ways of communication among bacterial colonies, swarming behaviour in bacteria is a vital phenomenon that has significance in signalling, virulence, pathogenicity, colonization, and antibiotic tolerance.…”