Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• substrate tolerance of MaDA for chemical probe design. After several attempts, Lei and co-workers designed and synthesized chemical probe 49 bearing a diazirine photoaffinity labelling unit with an alkyne tag on the phenolic hydroxy group of biosynthetic intermediate 44 (Scheme 5B). The treatment of

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• the MMFs specifically, we have developed a chemical probe that is capable of covalently binding to natural products containing furan moieties. Molecular probes are molecules that covalently bind to a compound of interest in order to make them easier to identify from the complex milieu of the cell

• determined that a ratio of 1:1 MeOH/H2O should be used as this solubilized the chemical probe most efficiently. Additionally, others have previously noted that polar solvents tend to benefit Diels–Alder reactions between furoic acids and maleimides [19][23]. Next, we looked at how different additives would

• aim to use these same conditions in cell extracts to probe for small molecules that may be unstable or volatile at higher temperatures. To test the chemical probe and determine the substrate scope of the reaction, we tested a small library of furans (Table 1). After each reaction was run, the samples

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• differences in the composition of cell membranes and presence of efflux pumps [9]. Specific protein labeling using a chemical probe can help to identify, characterize, and visualize target proteins [10][11]. The first chemical probe used for A-domains in NRPSs was reported by Marahiel et al. [8]. They

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• evaluation against GMD. Keywords: alginate; chemical probe; enzymatic synthesis; GDP-mannose dehydrogenase; sugar nucleotide; Introduction The opportunistic Gram-negative pathogen, Pseudomonas aeruginosa (PA), becomes the dominant pathogen in patients suffering from cystic fibrosis (CF) and causes a

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• 1 (or 17) which combines Notum inhibition with CNS penetration would be a valuable chemical probe for investigating the role of Notum in disease models. Keywords: brain penetration; 1-chloro-1,2-benziodoxol-3-one; electrophilic chlorination; LP-922056; Notum inhibitor; Introduction The Wnt

• of 1 (or 17) which combines Notum inhibition with CNS penetration would be a valuable chemical probe for investigating the role of Notum in disease models. This collection of data for amides 17a–r is shared as ‘open data’ to assist others in evaluating these results with the objective of solving this

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• substrate tunnel is indicated by a mesh. Structures and characteristics of hits against PqsD identified through different methods. HHQ and PQS analogues as PqsD inhibitors and chemical probe used for screening. Structure of PqsD-targeting biofilm inhibitor derived from linezolid. Fragment-based PqsE

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• against the active site specific chemical probe CA2. C) Concentration dependent competition experiment where the probe concentration is held constant and PqsD is pre-treated with varying inhibitor concentrations. D) Click chemistry control where the compounds were added shortly before CuII-salt addition

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• and reducing end functionality. Results and Discussion As part of a project on the synthesis of glycan fragments derived from arabinogalactan proteins (AGPs) [17][18], we sought to prepare a β1→6 linked galactan as a chemical probe. We elected to prepare the galactan with a pyrene-containing aglycone

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• with advancing basic in vitro and in vivo studies for testing new hypotheses in disease modulation. Within this report, the outcomes of two Sanford-Burnham projects for chemical probe discovery are discussed, highlighting five examples of thematic small-molecule chemical probes discovered through our

• chemical probe showed that it was not active (>30 μM) in more physiologically relevant HEK 293T and 697 pre-B cell lines. Therefore, an HTS campaign was initiated to identify compounds active in these specific cell subtypes by using the established HTS NF-κB reporter gene assay format. This included

• signaling, were discovered and optimized within the scope of the program. Tractable and efficient synthetic methods have been employed and are reported. Both NOD1 selective probes are now available as research tools either through the Sanford-Burnham Center or through commercial sources. Chemical probe

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• Michigan, Ann Arbor, MI 48109-1065, USA 10.3762/bjoc.9.12 Abstract The fluorophosphonate (FP) moiety attached to a biotin tag is a prototype chemical probe used to quantitatively analyze and enrich active serine hydrolases in complex proteomes in an approach called activity-based protein profiling (ABPP

Synthetic probes for the study of biological function

• Jeffrey Aubé

Beilstein J. Org. Chem. 2013, 9, 79–80, doi:10.3762/bjoc.9.10

• function. All three of these come together in the pursuit of new chemical probes for use in chemical biology. This Thematic Series highlights some of the numerous ways that molecular tools inform biological research. The choice of the phrase “chemical probe” was deliberately vague and indeed its meaning

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• Discussion Methyl cation affinities (MCA) The methyl cation (CH3+) is the smallest carbocation which is useful as a chemical probe for Lewis bases. The respective methyl cation affinity of a given Lewis base (LB) is obtained as the reaction enthalpy at 298.15 K and 1 bar pressure for the reaction shown in