Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• enzyme activity was assayed using H-Gly-Pro-1 as a substrate following the procedure described previously [23]. The reaction mixture (total 100 μL) contained 0.1 M Tris–HCl (pH 8.0), 10–50 μM substrate and 10–400 ng of the enzyme. The reaction was initiated by the addition of the enzyme solution

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• of the time course of Tr. Figure 5e demonstrates that the CRN is capable of producing sustained oscillations. We further processed the oscillating enzyme activity by coupling the multiple reactor modules, each with a specific chemical reaction. Figure 6 shows the feed forward designs that use an

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• oxidoreductases requires significant enzyme modifications. Specifically, codon optimization and the truncation of distinct domains which are responsible for, e.g., membrane localization can improve the enzyme activity. To date, identifying the necessary sequence segment for soluble expression in the bacterial

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• stabilised. Hence a turn-on of the CD fluorescence is indicative of enzyme activity. More recently, Galan et al. reported the 3 min one-step synthesis of blue-emitting CDs from glucosamine hydrochloride in the presence of TTDDA using microwave irradiation with QYs of up to 17% (Scheme 16) [46]. While most

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• been established [45]. It is also known that enzyme activity depends upon the local flexibility and solvent-exposed position of the target amino acid in the peptide [46]. Scheme 1 depicts the key design features, which are based on one of our previously published peptides [47], and the primary

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• crosslinked, these systems worked even better, enhancing enzyme activity [53], even under extreme chemical and thermal conditions [54]. As we were learning the rules for nanoparticle-biological interactions we started looking into applications for these self-assembled materials. Our first real success came

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• phosphate (IMP + H2O ↔ inosine + PO42−). This latter product is detected by using a malachite green assay and was quantified by the absorbance according to the phosphate concentration range. Most of the compounds were found to reduce the enzyme activity at high concentrations (>1 mM). However, only a

• which they block the enzyme activity. For this purpose, a SAR study was carried out by molecular docking. Attempts to make a direct correlation between the inhibitory activity and the gold-computed docking score (Table 2) were unsuccessful. Indeed, all compounds exhibited a similar score with a value

Highly stable and reusable immobilized formate dehydrogenases: Promising biocatalysts for in situ regeneration of NADH

• Barış Binay,
• Dilek Alagöz,
• Deniz Yildirim,
• Ayhan Çelik and
• S. Seyhan Tükel

Beilstein J. Org. Chem. 2016, 12, 271–277, doi:10.3762/bjoc.12.29

• preparations. The enzyme activity at 35 °C is taken as 100% for the each preparation. The experiments were run in triplicate. Thermal stability of free and immobilized FDH preparations at 35 °C. Thermal stability of free and immobilized FDH preparations at 50 °C. The reusability of immobilized FDHs. The

Bright molecules for sensing, computing and imaging: a tale of two once-troubled cities

• A. Prasanna de Silva

Beilstein J. Org. Chem. 2015, 11, 2774–2784, doi:10.3762/bjoc.11.298

• that the freshly-created fluorescence is killed off again (Figure 6). This is a fluorescence ‘off–on–off’ process driven by writing light dose. ‘Off–on–off’ processes are common [86][87][88][89][90][91][92][93][94], with enzyme activity as a function of pH and tunnel diode current as a function of

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• from Gaucher bearing N370/RecNcil mutations, being able to rescue the residual enzyme activity up to 1.25 fold [28]. These findings, together with the opportunity to easily functionalize the trihydroxypiperidine skeleton with an azido moiety at the terminal N-alkyl chain, prompted us to investigate the

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• decided not to normalise enzyme activity to expression levels in subsequent activity studies. Biotransformation reactions with library pools Biotransformations with pooled libraries and ethylbenzene (5) provided the average yield of alcohols (R,S)-9 up to 10%, which is comparable to previously published

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• , 12 was dissolved in an aqueous 2-(N-morpholine)ethanesulfonic acid (MES buffer) at pH 4.5 (enzyme activity optimum) and incubated with the enzyme in the presence of solubilizing 2,6-di-O-methyl-ß-cyclodextrin at 25 °C [51]. By virtue of analytical HPLC (UV detection based on Fmoc) and mass

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

• César A. Estévez,
• José Ramón Isasi,
• Eneko Larrañeta and
• Itziar Vélaz

Beilstein J. Org. Chem. 2014, 10, 3127–3135, doi:10.3762/bjoc.10.330

• ), taking 2 mL samples at different times; sample volumes were replaced with fresh medium. The lactase enzyme activity of the collected samples was analyzed according to the corresponding official USP monograph USP37–NF32, in duplicate for the gels and in quadruplicate for the tablets. An additional study

• addition, duplicate tests were performed with mixtures of lactase and α-CD and mixtures of lactase and Tetronic 90R4 to ascertain the possible influence of each component of the complex. Furthermore, the influence of storage time on enzyme activity was evaluated for T25a10 and T15a10 tablets after 3 months

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• subsequently followed by chiral HPLC. As a first attempt, Novozym 435-catalyzed KR of racemic alcohol (±)-3 was carried out (Table 1, entries 1–6). After series of experiments, the influence of various co-solvents could be summarized as the following row orders in terms of enzyme activity: pentane > n-hexane

• the investigated apolar solvents for Lipozyme TL IM catalyzed kinetic resolution of (±)-3, the best results were achieved in MTBE both in terms of enzyme activity and reaction enantioselectivity. The effect of the acyl donor on the kinetic resolution of (±)-3 A considerable number of fundamental

An integrated photocatalytic/enzymatic system for the reduction of CO₂ to methanol in bioglycerol–water

• Michele Aresta,
• Angela Dibenedetto,
• Tomasz Baran,
• Antonella Angelini,
• Przemysław Łabuz and
• Wojciech Macyk

Beilstein J. Org. Chem. 2014, 10, 2556–2565, doi:10.3762/bjoc.10.267

• most likely affects the enzyme activity by inducing structural modifications. In [7] a photocatalyst was used that operates on the border of the UV–vis spectrum. As described above, the goal of this research is to work in the visible-light range, possibly using direct irradiation with solar light

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• various types of bioactivity, e.g., herbicidal [12], inhibition of cell growth and enzyme activity [13][14][15][16][17][18], inhibition of voltage-gated sodium channels [19] and metabotropic glutamate receptor-5a (hmGluR5a) [20]. Consequently, our second aim was to extend the reaction to the preparation

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• towards a higher enzyme activity and/or to higher enzyme loadings in the immobilized state. For a residence time of 60 min (Figure 7) a yield of 32% was achieved, which is not substantially higher than found for the best yield using the immobilized enzyme under microreactor operation conditions. Studies

• above. Long term enzyme stability A continuous experiment was performed to study the long term stability of immobilized enzyme at 70 °C. The stability of Eupergit-bound TA (direct method) has already been discussed. The studies revealed that at 80 °C there is 20% loss of enzyme activity within 4 hours

• distribution present for the single-phase flow operation, different degrees of enzyme deactivation, and different degrees of enzyme activity – each being different for the three flow operations investigated. This gives room for future optimization. Above all, however, the existence of an equilibrium between

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• isolation and/or visualization (e.g., biotin or fluorophore) via click chemistry. This technology has been highly successful in profiling enzyme activity in living cells and even in whole organisms [21]. In ABPP, covalent linkage by the reactive functionality is usually dependent upon a particular enzymatic

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• measure of HDAC enzyme activity. The kinetics of AMC release was measured on a PolarStar fluorescence plate reader (BMG) with an excitation wavelength of 340 nm and an emission wavelength of 460 nm. Complete cleavage of deacetylated Boc-Lys-AMC by trypsin was achieved after about 10–15 min. The

• fluorescence intensity of the plateau was averaged over at least 5 min and normalized with respect to the percentage of enzyme activity. Finally, the normalized fluorescence intensities were plotted versus the concentration of test compounds and fitted to a four-parameter logistic model to calculate the IC50

Low-generation dendrimers with a calixarene core and based on a chiral C₂-symmetric pyrrolidine as iminosugar mimics

• Marco Marradi,
• Stefano Cicchi,
• Francesco Sansone,
• Alessandro Casnati and
• Andrea Goti

Beilstein J. Org. Chem. 2012, 8, 951–957, doi:10.3762/bjoc.8.107

• interactions [10], the effect of iminosugar-based multivalent inhibitors on enzyme activity is difficult to rationalise. However, the introduction of several copies of an N-alkyl analogue of iminosugar 1-deoxynojirimycin onto a fullerene ball [8] or onto β-cyclodextrin [9] afforded the first pieces of evidence

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• . Enzyme activity was determined from the linear reaction rate. Oxidation of 1a–d and 2 Standard oxidation reactions were performed in oxygen-saturated sodium phosphate buffer (50 mM, pH 6, saturated by flushing pure oxygen into the buffer for 10 min). Open glass vessels were used to allow easy oxygen

Conserved and species-specific oxylipin pathways in the wound-activated chemical defense of the noninvasive red alga Gracilaria chilensis and the invasive Gracilaria vermiculophylla

• Martin Rempt,
• Florian Weinberger,
• Katharina Grosser and
• Georg Pohnert

Beilstein J. Org. Chem. 2012, 8, 283–289, doi:10.3762/bjoc.8.30

• (Figure 1). Boiling prevents enzymatic reactions during work-up and results in the extraction of metabolites found in the intact algae (hereafter termed “intact”). Only trace levels of prostaglandins were detected in the wounded algae. The boiling of samples leads to a suppression of enzyme activity that

• grinding and incubation for 5 min at rt. In comparison, control runs with intact algal material that was boiled to prevent enzyme activity before extraction are given in (C) and (D). Total-ion-count (TIC) traces (ESI-negative mode) are shown; note: TIC normalized to 35000 counts in the wounded and to 500

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• inhibition: The larger the value of k1 the stronger the inhibitory effect of the nerve agent on the enzyme activity. By relating k1 to k1ref, the rate constant determined in the absence of the cyclodextrin, and to k1native, the rate constant determined in a preliminary assay in the absence of both

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• –liquid interface. The reactor was operated for 3 days and maintained ~80% of the initial enzyme activity. Only microbial contamination prevented a longer operation time of the process as it was carried out under nonsterile conditions. An overall space-time yield of 74.4 g L−1 day−1 was calculated with

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• exhibits no detectable enzyme activity [22], and so it is an intriguing question to investigate the nature of this OYHY…Oring interaction. MD simulations with the hybrid AM1/OPLS-AA/TIP3P method showed that both 4C1 chair and 2,5B boat conformers of phenyl β-xyloside remained stable in water during the