3,4,5-Trimethylphenol and Lewis Acid Dual-Catalyzed Cascade Ring-Opening/Cyclization: Direct Synthesis of Naphthalenes

A 3,4,5-trimethylphenol and Lewis acid dual-catalyzed cascade reaction of donor–acceptor (D–A) cyclopropanes via ring-opening and cyclization is developed. In this reaction, a phenolic compound was used as a covalent catalyst for the first time. Additionally, control experiments proved that 3,4,5-trimethylphenol completed the catalytic cycle by accomplishing the C–C bond cleavage. Using this strategy, a wide variety of substituted naphthalenes has been synthesized from D–A cyclopropanes in moderate to high yields under mild conditions

Rh(II) Catalyzed High Order Cycloadditions of 8‑Azaheptafulvenes with <i>N</i>‑Sulfonyl 1,2,3-Triazloes or α‑Oxo Diazocompounds

A novel strategy was developed for the application of Rh carbenes generated from readily accessible <i>N</i>-sulfonyl 1,2,3,-triazoles or diazocompouds in the high order cycloadditions, which offered an efficient route to a variety of N-containing medium-sized rings. The process provided a wide range of cyclo­hepta­[<i>b</i>]­pyrazine and cyclo­hepta­[<i>b</i>]­pyrrolone derivatives with high yields

Sc(OTf)₃ Catalyzed [4 + 2]-Annulation Reaction between Electron-Rich Phenols and Donor–Acceptor Cyclopropanes: Synthesis of Polysubstituted Dihydronaphthols

On the basis of the Lewis acid-catalyzed Friedel–Crafts alkylation between 1-acyl-2-arylcyclopropanecarboxylate esters and electron-rich phenols, a Sc­(OTf)₃ catalyzed cascade [4 + 2]-annulation reaction was developed for the direct synthesis of polysubstituted dihydronaphthols from phenols. In this reaction, the structure of products is dominated by the directing effect of the substituent groups on phenols. Meanwhile, a one-pot Friedel–Crafts alkylation/oxidative cyclization reaction was also developed for the synthesis of <i>spiro</i>-fused 2,5-cyclohexadienones

Reconstructing Genome-Wide Protein–Protein Interaction Networks Using Multiple Strategies with Homologous Mapping

<div><p>Background</p><p>One of the crucial steps toward understanding the biological functions of a cellular system is to investigate protein–protein interaction (PPI) networks. As an increasing number of reliable PPIs become available, there is a growing need for discovering PPIs to reconstruct PPI networks of interesting organisms. Some interolog-based methods and homologous PPI families have been proposed for predicting PPIs from the known PPIs of source organisms.</p><p>Results</p><p>Here, we propose a multiple-strategy scoring method to identify reliable PPIs for reconstructing the mouse PPI network from two well-known organisms: human and fly. We firstly identified the PPI candidates of target organisms based on homologous PPIs, sharing significant sequence similarities (joint <i>E</i>-value ≤ 1 × 10⁻⁴⁰), from source organisms using generalized interolog mapping. These PPI candidates were evaluated by our multiple-strategy scoring method, combining sequence similarities, normalized ranks, and conservation scores across multiple organisms. According to 106,825 PPI candidates in yeast derived from human and fly, our scoring method can achieve high prediction accuracy and outperform generalized interolog mapping. Experiment results show that our multiple-strategy score can avoid the influence of the protein family size and length to significantly improve PPI prediction accuracy and reflect the biological functions. In addition, the top-ranked and conserved PPIs are often orthologous/essential interactions and share the functional similarity. Based on these reliable predicted PPIs, we reconstructed a comprehensive mouse PPI network, which is a scale-free network and can reflect the biological functions and high connectivity of 292 KEGG modules, including 216 pathways and 76 structural complexes.</p><p>Conclusions</p><p>Experimental results show that our scoring method can improve the predicting accuracy based on the normalized rank and evolutionary conservation from multiple organisms. Our predicted PPIs share similar biological processes and cellular components, and the reconstructed genome-wide PPI network can reflect network topology and modularity. We believe that our method is useful for inferring reliable PPIs and reconstructing a comprehensive PPI network of an interesting organism.</p></div

Lewis Acid and (Hypo)iodite Relay Catalysis Allows a Strategy for the Synthesis of Polysubstituted Azetidines and Tetrahydroquinolines

A catalytic [3 + 1]-annulation reaction between cyclopropane 1,1-diester and aromatic amine is developed based on the relay catalysis strategy. Lewis acid-catalyzed nucleophilic ring opening of cyclopropane 1,1-diester with aromatic amine and (hypo)­iodite-catalyzed C–N bond formation are combined successfully in one reaction. Using this reaction, biologically important azetidines and tetrahydroquinolines can be prepared directly

The relationships between normalized ranks (<i>S_rank</i>) and orthologous interactions and joint-RSS scores on the YD set.

<p>(A) The distribution of orthologous interactions against normalized ranks. <i>S_rank</i> of 72% orthologous interactions of a template PPI is more than 0.9. (B) The <i>S_rank</i> scores of PPI candidates are correlated with their joint-<i>RSS</i> scores (<math><mrow><mi>j</mi><mi>o</mi><mi>i</mi><mi>n</mi><mi>t</mi><mo>−</mo><mi>R</mi><mi>S</mi><mi>S</mi><mo>=</mo><msqrt><mrow><mi>R</mi><mi>S</mi><msub><mi>S</mi><mrow><mi>B</mi><mi>P</mi></mrow></msub><mo>×</mo><mi>R</mi><mi>S</mi><msub><mi>S</mi><mrow><mi>C</mi><mi>C</mi></mrow></msub></mrow></msqrt></mrow></math>).</p

Reconstructed spliceosome sub-network of <i>M. musculus</i>.

<p>(A) The reconstructed spliceosome sub-network consists of including 99 proteins and 1,014 predicted PPIs, including 655 PPIs from only generalized interolog mapping methods (grey edges); 197 PPIs from only our method with <i>S</i> ≥ 2.3 (orange edges); and 162 PPIs from the overlap between generalized interolog mapping and our method (green edges). The sub-network consists of five structural complexes (i.e., U1-snRNP, U2-snRNP, U4/U6.U5 tri-snRNP, Prp19/CDC5L complex and 35S U5-snRNP) recorded in KEGG. Furthermore, three modules are recorded in the CORUM: Sm core, CDC5L core, and LSm2-8 complexes. The blue nodes are essential genes collected from the Mouse Genome Informatics database. (B) The two Sm core complexes are based on generalized interolog mapping (five PPIs) and our method with <i>S</i> ≥ 2.3 (14 PPIs). (C) The CDC5L core complex with five proteins and six PPIs based on our method (score <i>S</i> ≥ 2.3). </p

Overview of reconstructing genome-wide PPI networks using the multiple-strategy scoring method and homologous mapping.

<p>(A) Main procedure. (B) For a known PPI (e.g. EPHB2-ABL1) in the source organisms, the PPI candidates (joint <i>E</i>-value ≤ 1 × 10⁻⁴⁰) in the target organism are identified by searching the whole genome protein sequences using BLASTP. (C) These PPI candidates are scored by using the multiple-strategy scoring system (<i>S</i>), including the joint sequence similarity (<i>S_sim</i>), normalized rank (<i>S_rank</i>), and consensus (<i>S_con</i>). The candidates meeting the interaction score criterion (<i>S</i> ≥ 2.3) are considered as the predicted PPIs. (D) Part of the network is reconstructed by some predicted PPIs in the target organism (<i>M. musculus</i>) from known PPIs in two source organism (<i>H. sapiens</i> and D. <i>melanogaster</i>). The grey dashed lines denote the PPIs predicted from a single source organism. The red dashed lines denote the intersection PPIs predicted from both organisms. (E) The reconstructed mouse PPI network based on these predicted PPIs. (F) The distribution of degrees of this reconstructed mouse PPI network, which is a weak scale-free network (γ = 1.5). </p

Inferred axon growth pathway in <i>M. musculus</i> from <i>H. sapiens</i> and <i>D. melanogaster</i>.

<p>The axon growth pathways of two source organisms, <i>H. sapiens</i> (green nodes) and <i>D. melanogaster</i> (blue nodes), use PPIs recorded in five public databases. The pathway of <i>M. musculus</i> (orange nodes) is based on the PPIs experiment PPIs (five public databases) and predicted PPIs from <i>H. sapiens</i> (light green edges) and <i>D. melanogaster</i> (light blue edges). The PPIs (purple edges) are inferred from two organisms. The dashed lines denote the predicted PPIs which are not recorded in these five databases. </p

The relationship between the numbers of predicted PPIs with protein family sizes and protein lengths on YD and MD sets.

<p>The numbers of PPI candidates are highly correlated with (A) the number of homologous proteins (family size) and (B) protein sequence lengths of known PPI templates using generalized interologs mapping method (black lines) with joint sequence similarity (e.g., <i>E</i>-value ≤ 1 × 10⁻⁴⁰). Conversely, the numbers of predicted PPIs of our method (red lines) are lightly influenced by the protein family sizes and lengths. (C) For a known PPI, the number of homologous proteins in mouse is significantly greater than the one of yeast. For example, the number of homologous proteins of a zinc-finger (PF00096) protein in mouse and yeast are 275 and 24, respectively. </p