5561-87-5Relevant articles and documents
Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans
Jovanovic, Milos,Radivojevic, Jelena,O'Connor, Kevin,Blagojevic, Stevan,Begovic, Biljana,Lukic, Vera,Nikodinovic-Runic, Jasmina,Savic, Vladimir
supporting information, p. 209 - 217 (2019/03/23)
Rhamnolipids are biodegradable low toxic biosurfactants which exert antimicrobial and anti-biofilm properties. They have attracted much attention recently due to potential applications in areas of bioremediation, therapeutics, cosmetics and agriculture, however, the full potential of these versatile molecules is yet to be explored. Based on the facts that many naturally occurring lipopeptides are potent antimicrobials, our study aimed to explore the potential of replacing rhamnose in rhamnolipids with amino acids thus creating lipopeptides that would mimic or enhance properties of the parent molecule. This would allow not only for more economical and greener production but also, due to the availability of structurally different amino acids, facile manipulation of physico-chemical and biological properties. Our synthetic efforts produced a library of 43 lipopeptides revealing biologically more potent molecules. The structural changes significantly increased, in particular, anti-biofilm properties against Candida albicans, although surface activity of the parent molecule was almost completely abolished. Our findings show that the most active compounds are leucine derivatives of 3-hydroxy acids containing benzylic ester functionality. The SAR study demonstrated a further increase in activity with aliphatic chain elongation. The most promising lipopeptides 15, 23 and 36 at 12.5 μg/mL concentration allowed only 14.3%, 5.1% and 11.2% of biofilm formation, respectively after 24 h. These compounds inhibit biofilm formation by preventing adhesion of C. albicans to abiotic and biotic surfaces.
Controlling the Regioselectivity of Fatty Acid Hydroxylation (C10) at α- and β-Position by CYP152A1 (P450Bsβ) Variants
Hammerer, Lucas,Friess, Michael,Cerne, Jeyson,Fuchs, Michael,Steinkellner, Georg,Gruber, Karl,Vanhessche, Koenraad,Plocek, Thomas,Winkler, Christoph K.,Kroutil, Wolfgang
, p. 5642 - 5649 (2019/11/03)
Regioselective hydroxylation on inactivated C?H bonds is among the dream reactions of organic chemists. Cytochrome P450 enzymes (CYPs) perform this reaction in general with high regio- and stereoselectivity (e. g. for steroids as substrates). Furthermore, enzyme engineering may allow to tune the properties of the enzyme. Regioselective hydroxylation of shorter or linear molecules (fatty acids), however, remains challenging even with this enzyme class, due to the high similarity of the substrate's backbone carbons and their conformational flexibility. CYPs hydroxylating fatty acids selectively in the chemically more distinct α- or ω- position are well described. In contrast, selective in-chain hydroxylation of fatty acids lacks precedence. The peroxygenase CYP152A1 (P450Bsβ) is a family member that displays fatty acid hydroxylation at both, the α- and β-position, with preference for the α-position. Herein we report the influence of hydrophobic active site residues on the hydroxylation pattern of this enzyme. By site directed mutagenesis and combination of the libraries, double and triple mutation variants were identified, which hydroxylated decanoic acid (C10) with improved regio-selectivity in the β-position. Variants were identified with a 10-fold increase of the β-regioselectivity (expressed as α/β-ratio) compared to the wild type. In total 103 variants of CYP152A1 (P450Bsβ) were investigated.
Erratum: A Continuous, Fluorogenic Sirtuin 2 Deacylase Assay: Substrate Screening and Inhibitor Evaluation (Journal of Medicinal Chemistry (2016) 59 (1021-1031) DOI 10.1021/acs.jmedchem.5b01532)
Galleano, Iacopo,Schiedel, Matthias,Jung, Manfred,Madsen, Andreas S.,Olsen, Christian A.
supporting information, p. 2847 - 2847 (2016/04/10)
-
