1,721,102 research outputs found
PURINE NUCLEOSIDE PHOSPHORYLASES AS BIOCATALYSTS AND PHARMACOLOGICAL TARGETS
Full text linkA purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP) was successfully exploited to catalyze the “one-pot, one-enzyme” regio- and stereoselective transfer of β-D-ribose from a proper sugar donor (7-methylguanosine iodide) to a library of 6-substituted purine acceptors, resulting in the “in batch” synthesis of 24 ribonucleosides. Transglycosylation conversions confirmed the broad tolerance and the potential of AhPNP as biocatalyst, providing the necessary information to undertake the preparative synthesis of 6-modified purine nucleosides. [1]
AhPNP was then immobilized in a stainless steel column resulting in a stable and active bioreactor (AhPNP-IMER, Immobilized Enzyme Reactor) that, upon on-line connection to a semi-preparative HPLC system, was used to run transglycosylations in a flow mode. In such a set-up, biotransformation, on-line monitoring and product purification occurred in a single integrated platform, thus allowing the preparation of five nucleoside analogues at a mg scale (52-89% yield). [2]
As a step forward, a “one-pot, two-enzyme” strategy was applied by coupling AhPNP-IMER with an analogous bioreactor based on a uridine phosphorylase from Clostridium perfringens (CpUP), immobilized in a monolith column. The on-line apparatus obtained by connecting CpUP-IMER and AhPNP-IMER in series was tested in the synthesis of adenosine, 2’-deoxyadenosine and arabinosyladenine from uridine, 2’-deoxyuridine and arabinosyluracyl as sugar donors, respectively. The corresponding nucleobases were transformed into the products in 90-95% conversion over 1 h for the ribosyl and 2’-deoxyribosyl derivatives, and 20% conversion after 5 h for arabinosyladenine. [3]
Furthermore, a new LC-ESI-MS/MS method was set up to evaluate the inhibition activity of 8-substituted purine ribonucleosides toward the PNP from Mycobacterium tuberculosis (MtPNP), as well as the selectivity against the microbial enzyme with respect to the corresponding human one (HsPNP). The corresponding enzymatic assay, based on the phosphorolysis of inosine, proved to be very convenient in terms of time as well as of target amount. A small library of seven 8-substituted purine ribonucleosides were screened, not exerting any significant effect up to 1 mM, with 8-bromoguanosine and 8-methylaminoguanosine being the only exceptions at 500 mM as weak inhibitors. [4]
Finally, the chemical synthesis of a series of 8- and N2-substituted inosinic and guanylic acids as potential ligands of the human GPR17 receptor was carried out, starting from studies aided by molecular modeling on a homology model of the target. The molecules were prepared by 5’-phosphorylation of properly 8- and N2-modified/protected inosine or guanosine. Owing to the scarce nucleophilicity of the exocyclic NH2 group of guanosine, the 2-position of the purine ring was activated as a bromo derivative, whose displacement with the proper amine afforded the desired N2-alkylated products. On the contrary, N2-acylations were carried out through nitrogen functionalization with a proper acyl chloride or anhydride. An additional 2’,3’-O-isopropylidene group was inserted in all the N2-functionalized nucleotides. Binding assays on GPR17 will be carried out.
[1] D. Ubiali, C. F. Morelli, M. Rabuffetti, G. Cattaneo, I. Serra, T. Bavaro, A. M. Albertini, G. Speranza Curr. Org. Chem. 2015, 19, 2220-2225; [2] E. Calleri, G. Cattaneo, M. Rabuffetti, I. Serra, T. Bavaro, G. Massolini, G. Speranza, D. Ubiali Adv. Synth. Catal. 2015, 357, 2520-2528; [3] G. Cattaneo, M. Rabuffetti, G. Speranza, T. Kupfer, B. Peters, G. Massolini, D. Ubiali, E. Calleri Submitted 2017; [4] G. Cattaneo, D. Ubiali, E. Calleri, M. Rabuffetti, G. C. Hofner, K. T. Wanner, M. C. De Moraes, L. K. B Martinelli, D. S. Santos, G. Speranza Anal. Chim. Acta 2016, 943, 89-97
Chemoenzymatic Synthesis of Alkyl Glycoside Fatty Acid Esters and Investigation of their Emulsifying Properties
No full textSugar fatty acid esters (SFAEs) are non-ionic surfactants that are characterized by excellent surface and interfacial tension reduction capability, low toxicity, and biodegradability. These features make SFAEs extremely promising for industrial applications as emulsifiers in the cosmetic and food sectors.[1] Interestingly, SFAEs can be obtained from renewable resources (from industrial waste and biomass) by enzymatic and/or chemoenzymatic approaches, thus answering the need for evermore sustainable and circular chemistry.[2,3]
6-O-Lauroyl-, 6-O-palmitoyl- and 6-O-stearoyl-1-O-butyl glucopyranosides were enzymatically synthesized by reacting n-butyl glucoside with molten fatty acids in an easily scalable solvent-free system. Derivatization of glucose as an alkyl glucoside before the esterification reaction played a key role to circumvent the striking different solubility of glucose and fatty acids. The physico-chemical properties of these tensides, such as interfacial tension features, W/O emulsification capability and W/O stability over time were deeply investigated.[4]
References
1. N.S. Neta, J.A. Teixeira, L.R. Rodrigues, Crit. Rev. Food Sci. Nutr. 2015, 5, 595.
2. A.R. Alcántara, P. Domínguez de María, J.A. Littlechild, M. Schürmann, R.A. Sheldon, R. Wohlgemuth, ChemSusChem 2022, e202102709.
3. T. Keijer, Nat. Chem. 2019, 11, 190.
4. S. Sangiorgio, E. Pargoletti, M. Rabuffetti, M.S. Robescu, R. Semproli, D. Ubiali, G. Cappelletti, G. Speranza, under review
This work was financially supported by Cariplo Foundation (Italy) (call: “Circular Economy for a sustainable future 2020”, project BioSurf, ID 2020-1094)
Quantitative methodology for the assessment of visual exploratory and attentive skills on computer display.
No full textSeparation of free fatty acids and acylglycerols
No full textRice bran (RB), a low-value co-product of rice milling, contains about 20 % oil (rice bran oil, RBO). RBO is characterized by a high free fatty acids (FFA) content. This feature makes RBO unsuitable for processing into edible oil; however, it can be a valuable feedstock for the production of chemicals. In fact, a significant number of high-value products require FFA in their manufacturing. The production of FFA by hydrolysis of natural oils and fats is a very important aspect in the economic exploitation of these naturally produced renewable raw materials. Owing to the mild conditions of biocatalyzed processes, enzymatic hydrolysis of RBO appears an attractive approach to preserve the integrity of the oil components. Furthermore, enzyme specificity allows a better control of by-products formation. We here report the separation by flash chromatography of FFA and acylglycerols in a sample of RBO before and after the enzymatic hydrolysis. Results of the separation scale-up are also presented
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