Aleš Žula (Author), Izabela Będziak (Author), Danijel Kikelj (Author), Janez Ilaš (Author)

Abstract

Spumigins are marine natural products derived from cyanobacteria Nodularia spumigena, which mimics the structure of the D-Phe-Pro-Arg sequence and is crucial for binding to the active site of serine proteases thrombin and factor Xa. Biological evaluation of spumigins showed that spumigins with a (2S,4S)-4-methylproline central core represent potential lead compounds for the development of a new structural type of direct thrombin inhibitors. Herein, we represent synthesis and thrombin inhibitory activity of a focused library of spumigins analogues with indoline ring or L-proline as a central core. Novel compounds show additional insight into the structure and biological effects of spumigins. The most active analogue was found to be a derivative containing L-proline central core with low micromolar thrombin inhibitory activity.

Keywords

biokemija;morski proizvodi;naravni peptidi;inhibicija trombina;marine products;natural peptides;peptidomimetics;thrombin inhibition;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
Publisher: MDPI
UDC: 577
COBISS: 39787781 Link will open in a new window
ISSN: 1660-3397
Views: 277
Downloads: 148
Average score: 0 (0 votes)
Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: biokemija;morski proizvodi;naravni peptidi;inhibicija trombina;
Type (COBISS): Article
Pages: str. 1-19
Volume: ǂVol. ǂ16
Issue: ǂiss. ǂ11
Chronology: Nov. 2018
DOI: 10.3390/md16110413
ID: 12639651