Pd-Catalyzed Picolinamide-Directed C(sp2)-H Sulfonylation of Amino Acids/Peptides with Sodium Sulfinates.

This report describes a Pd-catalyzed picolinamide-directed site-selective C(sp2)-H sulfonylation of amino acids and peptides with sodium sulfinates in moderate to good yields. Sulfonylation of levodopa and dopamine drug molecules and late-stage directed peptide sulfonylation are studied for the first time. Broad substrate scope having various functionalities, late-stage drug modifications, and various post synthetic utilities such as chalcogenation, bromination, olefination, and arylation are potential advantages.

Relationship between the cost of illness and quality of life among adolescents with type 1 diabetes-a mixed method study.

Type 1 diabetes mellitus (T1DM) is a major problem worldwide that affects the quality of life, well-being of patients and their families. This study aimed to determine the relationship between the cost of illness and quality of life among patients with T1DM. A concurrent, parallel, mixed-method study of 113 adolescents with T1DM registered in public and private hospitals in the Mysore district was conducted by obtaining data related to the cost of illness and quality of life using a validated Diabetes-Specific Quality of Life (DSQoL) questionnaire. Thematic analysis was used to identify the themes. There was a significant association amonghealth insurance status, treatment facility type, catastrophic health expenditure (CHE), and cost of illness. The CHE proportion was32.7%. Financial sources for treatment were met primarily by borrowing money with interest (58 patients, 51.3%), followed by individualincome (40 patients, 35.3%), contributions from friends and relatives (10 patients, 8.8%), and selling of assets (5 patients, 4.4%). The monthly health expenditures of approximately 22 (19.46%) households were greater than their monthly incomes. There was a positive correlation (rvalue of 0.979) between the cost of treatment and the DSQoL score, and this correlation was statistically significant, with a p value < 0.001. The higher theDSQoL score was, the worse the quality of life and the worse the well-being of T1DM patients. Three themes were identified: the impact of financial cost on family coping, the impact of financial cost on seeking care and the emotional burden of financial cost. There was a statistically significant positive correlation between the cost of treatment and the DSQoLscore. Adolescents with T1DM who had greatertreatment costs had worseDSQoL, and significantly lower health expenses were observed among adolescentswho had health insurance. Cost of illness acts as a barrier to treatment and placesa burden on patients and their families.

The miR-29 family facilitates the activation of NK-cell immune responses by targeting the B7-H3 immune checkpoint in neuroblastoma.

Neuroblastoma (NB) is a highly aggressive pediatric cancer that originates from immature nerve cells, presenting significant treatment challenges due to therapy resistance. Despite intensive treatment, approximately 50% of high-risk NB cases exhibit therapy resistance or experience relapse, resulting in poor outcomes often associated with tumor immune evasion. B7-H3 is an immune checkpoint protein known to inhibit immune responses. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation. Our study aims to explore the impact of miRNAs on B7-H3 regulation, the anti-tumor immune response, and tumorigenicity in NB. Analysis of NB patients and patient-derived xenograft tumors revealed a correlation between higher B7-H3 expression and poorer patient survival. Notably, deceased patients exhibited a depletion of miR-29 family members (miR-29a, miR-29b, and miR-29c), which displayed an inverse association with B7-H3 expression in NB patients. Overexpression and knockdown experiments demonstrated that these miRNAs degrade B7-H3 mRNA, resulting in enhanced NK cell activation and cytotoxicity. In vivo, experiments provided further evidence that miR-29 family members reduce tumorigenicity, macrophage infiltration, and microvessel density, promote infiltration and activation of NK cells, and induce tumor cell apoptosis. These findings offer a rationale for developing more effective combination treatments that leverage miRNAs to target B7-H3 in NB patients.

Dysregulated cholinergic signaling inhibits oligodendrocyte maturation following demyelination.

Dysregulation of oligodendrocyte progenitor cell (OPC) recruitment and oligodendrocyte differentiation contribute to failure of remyelination in human demyelinating diseases such as multiple sclerosis (MS). Deletion of muscarinic receptor enhances OPC differentiation and remyelination. However, the role of ligand-dependent signaling versus constitutive receptor activation is unknown. We hypothesized that dysregulated acetylcholine (ACh) release upon demyelination contributes to ligand mediated activation hindering myelin repair. Following chronic cuprizone induced demyelination (male and female mice), we observed a 2.5-fold increase in ACh concentration. This increase in ACh concentration could be attributed to increased ACh synthesis or decreased acetylcholinesterase (AChE) / butyrylcholinesterase (BChE) mediated degradation. Using ChAT reporter mice, we identified increased ChAT-GFP expression following both lysolecithin and cuprizone demyelination. ChAT-GFP expression was upregulated in a subset of injured and uninjured axons following intraspinal lysolecithin induced demyelination. In cuprizone demyelinated corpus callosum, ChAT-GFP was observed in Gfap+ astrocytes and axons indicating the potential for neuronal and astrocytic ACh release. BChE expression was significantly decreased in the corpus callosum following cuprizone demyelination. This decrease was due to the loss of myelinating oligodendrocytes which were the primary source of BChE. To determine the role of ligand mediated muscarinic signaling following lysolecithin injection, we administered neostigmine, a cholinesterase inhibitor, to artificially raise ACh. We identified a dose-dependent decrease in mature oligodendrocyte density with no effect on OPC recruitment. Together, these results support a functional role of ligand mediated activation of muscarinic receptors following demyelination and suggest that dysregulation of ACh homeostasis directly contributes to failure of remyelination in MS.Significance Statement Demyelinating diseases like Multiple Sclerosis are characterized by failure of remyelination. Oligodendrocyte progenitor cell (OPC) recruitment and differentiation are crucial aspects for remyelination to occur. Here we show that increased acetylcholine (ACh) contributes to activation of muscarinic receptors that inhibit OPC differentiation. Increased choline acetyltransferase synthesis following demyelination was observed in axons and astrocytes suggestive of a potential for acetylcholine synthesis and release. The increase in ACh levels following demyelination was largely due to reduction of oligodendrocyte derived butyrylcholinesterase that modulates ACh concentration. Development of cell specific esterase stimulator to restore ACh levels may serve as an approach towards inhibiting ongoing demyelination and neurodegeneration.

Ru(II)-Catalyzed C(sp2)-H Activation Annulation: Synthesis of Fluorescent Benzoisoquinolonyl Acetate/Peptides from N-Arylamides and Ethyne at Room Temperature.

Benzoisoquinolones are aryl ring extended isoquinolinone derivatives, which are constituents of alkaloid natural products. This report describes the synthesis of novel benzoisoquinolone amino acid/peptide derivatives from the respective N-aryl amino esters/peptides through Ru-catalyzed C(sp2)-H annulation at room temperature. The N-terminal amide acts as an intrinsic directing group and coordinates with the active Ru(II) catalyst for the C-H bond activation and annulation of the aryl ring to produce benzoisoqunolone derivatives. Importantly, these benzoisoquinolinones exhibit fluorescence (QY ∼35%) in protic polar solvents, possibly due to charge transfer, and exhibit cell internalization to the cell nucleus without any significant cytotoxicity to human cell lines (HEK293T). Hence, our results are exceptional to transform standard amino acids/peptides into fluorescent peptides at room temperature in the late stage, which could be applicable for tracking specific target peptides by fluorescence microscopy.

SAP30, an oncogenic driver of progression, poor survival, and drug resistance in neuroblastoma.

Neuroblastoma is the most devastating extracranial solid malignancy in children. Despite an intense treatment regimen, the prognosis for high-risk neuroblastoma patients remains poor, with less than 40% survival. So far, MYCN amplification status is considered the most prognostic factor but corresponds to only ∼25% of neuroblastoma patients. Therefore, it is essential to identify a better prognosis and therapy response marker in neuroblastoma patients. We applied robust bioinformatic data mining tools, such as weighted gene co-expression network analysis, cisTarget, and single-cell regulatory network inference and clustering on two neuroblastoma patient datasets. We found Sin3A-associated protein 30 (SAP30), a driver transcription factor positively associated with high-risk, progression, stage 4, and poor survival in neuroblastoma patient cohorts. Tumors of high-risk neuroblastoma patients and relapse-specific patient-derived xenografts showed higher SAP30 levels. The advanced pharmacogenomic analysis and CRISPR-Cas9 screens indicated that SAP30 essentiality is associated with cisplatin resistance and further showed higher levels in cisplatin-resistant patient-derived xenograft tumor cell lines. Silencing of SAP30 induced cell death in vitro and led to a reduced tumor burden and size in vivo. Altogether, these results indicate that SAP30 is a better prognostic and cisplatin-resistance marker and thus a potential drug target in high-risk neuroblastoma.

Synthesis of R-GABA Derivatives via Pd(II) Catalyzed Enantioselective C(sp3)-H Arylation and Virtual Validation with GABAB1 Receptor for Potential leads.

GABA (γ-amino butyric acid) analogues like baclofen, tolibut, phenibut, etc., are well-known GABAB1 inhibitors and pharmaceutically important drugs. However, there is a huge demand for more chiral GABA aryl analogues with promising pharmacological actions. Here, we demonstrate the chiral ligand acetyl-protected amino quinoline (APAQ) mediated enantioselective synthesis of GABAB1 inhibitor drug scaffolds from easily accessible GABA via Pd-catalyzed C(sp3)-H activation. The synthetic methodology shows moderate to good yields, up to 74% of ee. We have successfully demonstrated the deprotection and removal of the directing group to synthesize R-tolibut in 86% yield. Further, we employed computation to probe the binding of R-GABA analogues to the extracellular domain of the human GABAB1 receptor. Our Rosetta-based molecular docking calculations show better binding for four R-enantiomers of GABA analogues than R-baclofen and R-phenibut. In addition, we employed GROMACS MD simulations and MMPB(GB)SA calculations to identify per-residue contribution to binding free energy. Our computational results suggest analogues (3R)-4-amino-3-(3,4-dimethylphenyl) butanoic acid, (3R)-4-amino-3-(3-fluorophenyl) butanoic acid, (3R)-3-(4-acetylphenyl)-4-aminobutanoic acid, (3R)-4-amino-3-(4-methoxyphenyl) butanoic acid, and (3R)-4-amino-3-phenylbutanoic acid are potential leads which could be synthesized from our methodology reported here.

Marinopyrrole derivative MP1 as a novel anti-cancer agent in group 3 MYC-amplified Medulloblastoma.

BACKGROUND: Medulloblastoma (MB) patients with MYC oncogene amplification or overexpression exhibit extremely poor prognoses and therapy resistance. However, MYC itself has been one of the most challenging targets for cancer treatment. Here, we identify a novel marinopyrrole natural derivative, MP1, that shows desirable anti-MYC and anti-cancer activities in MB. METHODS: In this study, using MYC-amplified (Group 3) and non-MYC amplified MB cell lines in vitro and in vivo, we evaluated anti-cancer efficacies and molecular mechanism(s) of MP1. RESULTS: MP1 significantly suppressed MB cell growth and sphere counts and induced G2 cell cycle arrest and apoptosis in a MYC-dependent manner. Mechanistically, MP1 strongly downregulated the expression of MYC protein. Our results with RNA-seq revealed that MP1 significantly modulated global gene expression and inhibited MYC-associated transcriptional targets including translation/mTOR targets. In addition, MP1 inhibited MYC-target metabolism, leading to declined energy levels. The combination of MP1 with an FDA-approved mTOR inhibitor temsirolimus synergistically inhibited MB cell growth/survival by downregulating the expression of MYC and mTOR signaling components. Our results further showed that as single agents, both MP1 and temsirolimus, were able to significantly inhibit tumor growth and MYC expression in subcutaneously or orthotopically MYC-amplified MB bearing mice. In combination, there were further anti-MB effects on the tumor growth and MYC expression in mice. CONCLUSION: These preclinical findings highlight the promise of marinopyrrole MP1 as a novel MYC inhibition approach for MYC-amplified MB.

Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 µg/mL and standard deviation of 0.43 µg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 µg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

Comparative transcriptome analysis of two contrasting genotypes provides new insights into the drought response mechanism in pigeon pea (Cajanus cajan L. Millsp.).

BACKGROUND: Despite plant's ability to adapt and withstand challenging environments, drought poses a severe threat to their growth and development. Although pigeon pea is already quite resistant to drought, the prolonged dehydration induced by the aberrant climate poses a serious threat to their survival and productivity. OBJECTIVE: Comparative physiological and transcriptome analyses of drought-tolerant (CO5) and drought-sensitive (CO1) pigeon pea genotypes subjected to drought stress were carried out in order to understand the molecular basis of drought tolerance in pigeon pea. METHODS: The transcriptomic analysis allowed us to examine how drought affects the gene expression of C. cajan. Using bioinformatics tools, the unigenes were de novo assembled, annotated, and functionally evaluated. Additionally, a homology-based sequence search against the droughtDB database was performed to identify the orthologs of the DEGs. RESULTS: 1102 potential drought-responsive genes were found to be differentially expressed genes (DEGs) between drought-tolerant and drought-sensitive genotypes. These included Abscisic acid insensitive 5 (ABI5), Nuclear transcription factor Y subunit A-7 (NF-YA7), WD40 repeat-containing protein 55 (WDR55), Anthocyanidin reductase (ANR) and Zinc-finger homeodomain protein 6 (ZF-HD6) and were highly expressed in the tolerant genotype. Further, GO analysis revealed that the most enriched classes belonged to biosynthetic and metabolic processes in the biological process category, binding and catalytic activity in the molecular function category and nucleus and protein-containing complex in the cellular component category. Results of KEGG pathway analysis revealed that the DEGs were significantly abundant in signalling pathways such as plant hormone signal transduction and MAPK signalling pathways. Consequently, in our investigation, we have identified and validated by qPCR a group of genes involved in signal reception and propagation, stress-specific TFs, and basal regulatory genes associated with drought response. CONCLUSION: In conclusion, our comprehensive transcriptome dataset enabled the discovery of candidate genes connected to pathways involved in pigeon pea drought response. Our research uncovered a number of unidentified genes and transcription factors that could be used to understand and improve susceptibility to drought.

PRMT5 as a Potential Therapeutic Target in MYC-Amplified Medulloblastoma.

MYC amplification or overexpression is most common in Group 3 medulloblastomas and is positively associated with poor clinical outcomes. Recently, protein arginine methyltransferase 5 (PRMT5) overexpression has been shown to be associated with tumorigenic MYC functions in cancers, particularly in brain cancers such as glioblastoma and medulloblastoma. PRMT5 regulates oncogenes, including MYC, that are often deregulated in medulloblastomas. However, the role of PRMT5-mediated post-translational modification in the stabilization of these oncoproteins remains poorly understood. The potential impact of PRMT5 inhibition on MYC makes it an attractive target in various cancers. PRMT5 inhibitors are a promising class of anti-cancer drugs demonstrating preclinical and preliminary clinical efficacies. Here, we review the publicly available preclinical and clinical studies on PRMT5 targeting using small molecule inhibitors and discuss the prospects of using them in medulloblastoma therapy.

Pd-Catalyzed Picolinamide-Directed Late-Stage Chalcogenation of Tryptophan-Containing Peptides.

This report describes the Pd-catalyzed late-stage chalcogenation of tryptophan-containing peptides with disulfides/diselenides in moderate to good yields. It comprises broad substrate scope, functional group diversity, late-stage modification of drug molecules, and various valuable synthetic transformations, including room temperature easy removal of the picolinamide auxiliary, which could be applicable to tune the structure and function of peptides.

N-Salicyl-AAn-picolamide Foldameric Peptides Exhibit Quorum Sensing Inhibition of Pseudomonas aeruginosa (PA14).

An organic acid, salicylic acid, and its derivatives are constituents of various natural products possessing remarkable bioactivity. O-Acetyl salicylate (aspirin) is a well-known life-saving drug. Its peptide derivative salicylamide has also been explored in the designing of peptide-based therapeutic drugs. An organic base, picolylamine has been recently explored for designing diagnostic probes. However, both the acid and base have common features as metal chelating with coordinating metals. Thus, these scaffolds could be used for designing inhibitors of various metalloenzymes. Their characteristic properties encourage us to design peptides containing both scaffolds (salicylic acid and picolylamine) at opposite terminals. So far there is no report available on such conjugated peptides. This report describes the synthesis, conformational analysis, and biochemical assessment of rationally designed N-salicyl-AAn-picolamide peptides. Pleasantly, we have obtained the crystal structures of representative peptides that confirm their roles in conformational changes. Our biological assessment as quorum sensing inhibitors has revealed that their di/tripeptides inhibit quorum sensing of the pathogenic bacterium PA14 strain. Hence, these peptides have promising foldameric and therapeutic values.

Right place, no trace: A case report of postintubation bronchospasm.

Evidence suggests obesity correlates with airway hyperreactivity, which can result in severe bronchospasm. This report presents a 31-year-old female with a high body mass index who presented for a laparoscopic hysterectomy and bilateral salpingo-oophorectomy. She had no past medical or atopic history. After induction of anaesthesia and intubation, O2 saturation fell with no CO2 trace, breathing sounds or chest rise. Despite confirming endotracheal tube position by video laryngoscopy, the CO2 trace remained flat and mechanical ventilation was difficult with high airway pressures. Blood pressure was stable with no mucocutaneous signs of anaphylaxis. Administration of 100% O2, bronchodilators and steroids improved ventilation and oxygenation with a return of a CO2 trace. The operation was postponed. Prior to her subsequent surgery, the patient was premedicated with inhaled steroids and long-acting beta agonist with an uneventful induction and intubation. Giving a rising obese population, this case report aims to educate anaesthetists and anaesthetic practitioners as to the presentation, risk factors, mechanisms and management of uncommon, life-threatening postintubation bronchospasm.

Phylogenomic Analysis of micro-RNA Involved in Juvenile to Flowering-Stage Transition in Photophilic Rice and Its Sister Species.

Vegetative to reproductive phase transition in phototropic plants is an important developmental process and is sequentially mediated by the expression of micro-RNA MIR172. To obtain insight into the evolution, adaptation, and function of MIR172 in photophilic rice and its wild relatives, we analyzed the genescape of a 100 kb segment harboring MIR172 homologs from 11 genomes. The expression analysis of MIR172 revealed its incremental accumulation from the 2-leaf to 10-leaf stage, with maximum expression coinciding with the flag-leaf stage in rice. Nonetheless, the microsynteny analysis of MIR172s revealed collinearity within the genus Oryza, but a loss of synteny was observed in (i) MIR172A in O. barthii (AA) and O. glaberima (AA); (ii) MIR172B in O. brachyantha (FF); and (iii) MIR172C in O. punctata (BB). Phylogenetic analysis of precursor sequences/region of MIR172 revealed a distinct tri-modal clade of evolution. The genomic information generated in this investigation through comparative analysis of MIRNA, suggests mature MIR172s to have evolved in a disruptive and conservative mode amongst all Oryza species with a common origin of descent. Further, the phylogenomic delineation provided an insight into the adaptation and molecular evolution of MIR172 to changing environmental conditions (biotic and abiotic) of phototropic rice through natural selection and the opportunity to harness untapped genomic regions from rice wild relatives (RWR).

Synthesis of N-isoindolinonyl peptides via Pd-catalyzed C(sp2)-H olefination-activation and their conformational studies.

Isoindolinone is a constituent of several natural products that show a wide range of bioactivity, such as anticancer, antimicrobial, antiviral and anti-inflammatory properties. It would be interesting to explore the carbonyl group (H-bond acceptor) of isoindolinone and its structural and conformational changes. However, the synthesis of isoindolinone-comprising peptides in short steps is challenging. Herein, we have developed a synthetic methodology for introducing the isoindolinone residue to peptides via Pd-catalyzed C(sp2)-H activation/olefination, and demonstrated the conformational changes owing to the isoindolinone scaffold. Hence, isoindolinonyl peptides provide an avenue for the synthesis of novel foldamers and therapeutic agents.

STAT3 Inhibition Attenuates MYC Expression by Modulating Co-Activator Recruitment and Suppresses Medulloblastoma Tumor Growth by Augmenting Cisplatin Efficacy In Vivo.

MB is a common childhood malignancy of the central nervous system, with significant morbidity and mortality. Among the four molecular subgroups, MYC-amplified Group 3 MB is the most aggressive type and has the worst prognosis due to therapy resistance. The present study aimed to investigate the role of activated STAT3 in promoting MB pathogenesis and chemoresistance via inducing the cancer hallmark MYC oncogene. Targeting STAT3 function either by inducible genetic knockdown (KD) or with a clinically relevant small molecule inhibitor reduced tumorigenic attributes in MB cells, including survival, proliferation, anti-apoptosis, migration, stemness and expression of MYC and its targets. STAT3 inhibition attenuates MYC expression by affecting recruitment of histone acetyltransferase p300, thereby reducing enrichment of H3K27 acetylation in the MYC promoter. Concomitantly, it also decreases the occupancy of the bromodomain containing protein-4 (BRD4) and phosphoSer2-RNA Pol II (pSer2-RNAPol II) on MYC, resulting in reduced transcription. Importantly, inhibition of STAT3 signaling significantly attenuated MB tumor growth in subcutaneous and intracranial orthotopic xenografts, increased the sensitivity of MB tumors to cisplatin, and improved the survival of mice bearing high-risk MYC-amplified tumors. Together, the results of our study demonstrate that targeting STAT3 may be a promising adjuvant therapy and chemo-sensitizer to augment treatment efficacy, reduce therapy-related toxicity and improve quality of life in high-risk pediatric patients.

Drought and Oxidative Stress in Flax (Linum usitatissimum L.) Entails Harnessing Non-Canonical Reference Gene for Precise Quantification of qRT-PCR Gene Expression.

Flax (Linum usitatissimum L.) is a self-pollinating, annual, diploid crop grown for multi-utility purposes for its quality oil, shining bast fiber, and industrial solvent. Being a cool (Rabi) season crop, it is affected by unprecedented climatic changes such as high temperature, drought, and associated oxidative stress that, globally, impede its growth, production, and productivity. To precisely assess the imperative changes that are inflicted by drought and associated oxidative stress, gene expression profiling of predominant drought-responsive genes (AREB, DREB/CBF, and ARR) was carried out by qRT-PCR. Nevertheless, for normalization/quantification of data obtained from qRT-PCR results, a stable reference gene is mandatory. Here, we evaluated a panel of four reference genes (Actin, EF1a, ETIF5A, and UBQ) and assessed their suitability as stable reference genes for the normalization of gene expression data obtained during drought-induced oxidative stress in flax. Taking together, from the canonical expression of the proposed reference genes in three different genotypes, we report that EF1a as a stand-alone and EF1a and ETIF5A in tandem are suitable reference genes to be used for the real-time visualization of cellular impact of drought and oxidative stress on flax.

A new transient directing group diethoxyethyl-L-proline facilitates ortho-arylation of aryl-amines/-amino acids via Pd-catalyzed C(sp2)-H activation.

Mono-ortho-arylated arylamines are constituents of various natural products but their syntheses are challenging. This report describes a new synthetic methodology for the ortho-arylation of arylamines and α-aromatic amino acids (phenylglycine and phenylalanine) through a Pd-catalyzed C(sp2)-H activation using the synthetic transient directing group diethoxyethyl-L-proline (DEP). A catalytic amount of diethoxyethyl-L-proline is sufficient to form mono-arylated arylamines as the major products using aryliodides. This method could be useful for the synthesis of various biphenyl amines and novel peptidomimetics.

Tropolone-Conjugated DNA: A Fluorescent Thymidine Analogue Exhibits Solvatochromism, Enzymatic Incorporation into DNA and HeLa Cell Internalization.

Tropolone is a non-benzenoid aromatic scaffold with unique photophysical and metal-chelating properties. Recently, it has been conjugated with DNA, and the photophysical properties of this conjugate have been explored. Tropolonyl-deoxyuridine (tr-dU) is a synthetic fluorescent DNA nucleoside analogue that exhibits pH-dependent emissions. However, its solvent-dependent fluorescence properties are unexplored owing to its poor solubility in most organic solvents. It would be interesting to incorporate it into DNA primer enzymatically. This report describes the solvent-dependent fluorescence properties of the silyl-derivative, and enzymatic incorporation of its triphosphate analogue. For practical use, its cell-internalization and cytotoxicity are also explored. tr-dU nucleoside was found to be a potential analogue to design DNA probes and can be explored for various therapeutic applications in the future.