ABSTRACT
We report the first biocatalytic modification of sesquiterpene lactones (STLs) found in the chicory plants, specifically lactucin (Lc), 11ß,13-dihydrolactucin (DHLc), lactucopicrin (Lp), and 11ß,13-dihydrolactucopicrin (DHLp). The selective O-acylation of their primary alcohol group was carried out by the lipase B from Candida antarctica (CAL-B) using various aliphatic vinyl esters as acyl donors. Perillyl alcohol, a simpler monoterpenoid, served as a model to set up the desired O-acetylation reaction by comparing the use of acetic acid and vinyl acetate as acyl donors. Similar conditions were then applied to DHLc, where five novel ester chains were selectively introduced onto the primary alcohol group, with conversions going from >99 % (acetate and propionate) to 69 % (octanoate). The synthesis of the corresponding O-acetyl esters of Lc, Lp, and DHLp was also successfully achieved with near-quantitative conversion. Molecular docking simulations were then performed to elucidate the preferred enzyme-substrate binding modes in the acylation reactions with STLs, as well as to understand their interactions with crucial amino acid residues at the active site. Our methodology enables the selective O-acylation of the primary alcohol group in four different STLs, offering possibilities for synthesizing novel derivatives with significant potential applications in pharmaceuticals or as biocontrol agents.
Subject(s)
Cichorium intybus , Sesquiterpenes , Esters/chemistry , Molecular Docking Simulation , Acylation , LactonesABSTRACT
For powder catalyst characterization, Fourier Transform Infrared (FTIR), Raman, and X-Ray Fluorescence (XRF) spectrometers and X-Ray Diffraction (XRD) are available in high-throughput (HT) configurations, for example at the REALCAT platform to sequentially analyse multiple sets of samples. To remove the bottleneck resulting from the use of different sample holders for each equipment, a unique multi-well plate was developed. This paper details the design of such a plate including the selection of the fabrication material and the plate dimensioning based on the study of the 4 different physical interactions between matter and electromagnetic radiations for the aforementioned techniques. This new plate consists of a holder for removable wells enabling the avoidance of cross-contamination between samples. Raman, a focusing technique, has no strict constraint on the plate design. The number of wells, their geometry, spacing and dimensions were adjusted to deal with the constraints of IR optics. The well depth was set according to the XRF maximum penetration depth in the sample. The well diameter was optimized in order to obtain from the X-ray spot size the maximum achievable intensity. Poly-methyl-methacrylate (PMMA) was chosen as the material for the new plate due to its amorphous structure (no peak in XRD analysis) and ease with which it can be cut by a laser. Finally, the flatness of the multi-well plate was validated on the most challenging instrument: XRD. This new plate allows fast sample filling/preparation, requires small quantities of catalyst (50 to 80 mg) in each well and is compatible and convenient for HT experimentation.
ABSTRACT
The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi).
