Use of novel taurine-chitosan mediated liposomes for enhancing the oral absorption of doxorubicin via the TAUT transporter.

Our research aimed to enhance the oral bioavailability of doxorubicin hydrochloride (DOX·HCl) while minimizing the potential for myocardial toxicity. To achieve this goal, we developed a new method that utilizes a coating material to encapsulate the drug in liposomes, which can specifically target intestinal taurine transporter proteins. This coating material, TAU-CS, was created by combining taurine with chitosan. We characterized TAU-CS using various methods, including 1H NMR, FT-IR, and scanning electron microscopy (SEM). The resulting liposomes exhibited a regular spherical morphology, with a particle size of 195.7 nm, an encapsulation efficiency of 91.23 %, and a zeta potential of +11.65 mV. Under simulated gastrointestinal conditions, TAU-CS/LIP@DOX·HCl exhibited good stability and slow release. Pharmacokinetic studies revealed that, compared with DOX·HCl, TAU-CS/LIP@DOX·HCl had a relative bioavailability of 342 %. Intracellular uptake, immunofluorescence imaging, and permeation assays confirmed that the taurine transporter protein mediates the intestinal uptake of these liposomes. Our study suggested that liposomes coated with TAU-CS could serve as an effective oral delivery system and that targeting the taurine transporter protein shows promise in enhancing drug absorption.

Combining Transcriptome and Whole Genome Re-Sequencing to Screen Disease Resistance Genes for Wheat Dwarf Bunt.

Wheat dwarf bunt is a damaging disease caused by Tilletia controversa Kühn (TCK). Once the disease infects wheat, it is difficult to control and will significantly reduce wheat output and quality. RNA sequencing and whole genome re-sequencing were used to search for potential TCK resistance genes in Yili 053 (sensitive variety) and Zhongmai 175 (moderately resistant variety) in the mid-filling, late-filling, and maturity stages. The transcriptomic analysis revealed 11 potential disease resistance genes. An association analysis of the findings from re-sequencing found nine genes with single nucleotide polymorphism mutations. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that three up-regulated genes were involved in the synthesis of benzoxazinone and tryptophan metabolism. Additionally, quantitative real-time polymerase chain reaction confirmed the RNA sequencing results. The results revealed novel TCK resistance genes and provide a theoretical basis for researching the function of resistance genes and molecular breeding.

Alicyclic Ring Size Variation of 4-Phenyl-2-naphthoic Acid Derivatives as P2Y14 Receptor Antagonists.

P2Y14 receptor (P2Y14R) is activated by extracellular UDP-glucose, a damage-associated molecular pattern that promotes inflammation in the kidney, lung, fat tissue, and elsewhere. Thus, selective P2Y14R antagonists are potentially useful for inflammatory and metabolic diseases. The piperidine ring size of potent, competitive P2Y14R antagonist (4-phenyl-2-naphthoic acid derivative) PPTN 1 was varied from 4- to 8-membered rings, with bridging/functional substitution. Conformationally and sterically modified isosteres included N-containing spirocyclic (6-9), fused (11-13), and bridged (14, 15) or large (16-20) ring systems, either saturated or containing alkene or hydroxy/methoxy groups. The alicyclic amines displayed structural preference. An α-hydroxyl group increased the affinity of 4-(4-((1R,5S,6r)-6-hydroxy-3-azabicyclo[3.1.1]heptan-6-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoic acid 15 (MRS4833) compared to 14 by 89-fold. 15 but not its double prodrug 50 reduced airway eosinophilia in a protease-mediated asthma model, and orally administered 15 and prodrugs reversed chronic neuropathic pain (mouse CCI model). Thus, we identified novel drug leads having in vivo efficacy.

Design and Analysis of Lithium-Niobate-Based Laterally Excited Bulk Acoustic Wave Resonator with Pentagon Spiral Electrodes.

In this paper, we present a comprehensive study on the propagation and dispersion characteristics of A1 mode propagating in Z-cut LiNbO3 membrane. The A1 mode resonators with pentagon spiral electrodes utilizing Z-cut lithium niobate (LiNbO3) thin film are designed and fabricated. The proposed structure excites the A1 mode waves in both x- and y-direction by utilizing both the piezoelectric constants e24 and e15 due to applying voltage along both the x- and y-direction by arranging pentagon spiral electrode. The fabricated resonator operates at 5.43 GHz with no spurious mode and effective electromechanical coupling coefficient (Keff2) of 21.3%, when the width of electrode is 1 µm and the pitch is 5 µm. Moreover, we present a comprehensive study of the effect of different structure parameters on resonance frequency and Keff2 of XBAR. The Keff2 keeps a constant with varied thickness of LiNbO3 thin film and different electrode rotation angles, while it declines with the increase of p from 5 to 20 µm. The proposed XBAR with pentagon spiral electrodes realize high frequency response with no spurious mode and tunable Keff2, which shows promising prospects to satisfy the needs of various 5 G high-band application.

New paradigms in purinergic receptor ligand discovery.

The discovery and clinical implementation of modulators of adenosine, P2Y and P2X receptors (comprising nineteen subtypes) have progressed dramatically in ∼50 years since Burnstock's definition of purinergic signaling. Although most clinical trials of selective ligands (agonists and antagonists) of certain purinergic receptors failed, there is a renewed impetus to redirect efforts to new disease conditions and the discovery of more selective or targeted compounds with potentially reduced side effects, such as biased GPCR agonists. The elucidation of new receptor and enzyme structures is steering rational design of potent and selective agonists, antagonists, allosteric modulators and inhibitors. A2A adenosine receptor (AR) antagonists are being applied to neurodegenerative conditions and cancer immunotherapy. A3AR agonists have potential for treating chronic inflammation (e.g. psoriasis), stroke and pain, as well as cancer. P2YR modulators are being considered for treating inflammation, metabolic disorders, acute kidney injury, cancer, pain and other conditions, often with an immune mechanism. ADP-activated P2Y12R antagonists are widely used as antithrombotic drugs, while their repurposing toward neuroinflammation is considered. P2X3 antagonists have been in clinical trials for chronic cough. P2X7 antagonists have been in clinical trials for inflammatory diseases and depression (compounds that penetrate the blood-brain barrier). Thus, purinergic signaling is now recognized as an immense regulatory system in the body for rebalancing tissues and organs under stress, which can be adjusted by drug intervention for therapeutic purposes. The lack of success of many previous clinical trials can be overcome given more advanced pharmacokinetic and pharmacodynamic approaches, including structure-based drug design, prodrugs and biased signaling. This article is part of the Special Issue on "Purinergic Signaling: 50 years".

Aluminum Nitride-Based Adjustable Effective Electromechanical Coupling Coefficient Film Bulk Acoustic Resonator.

The arrival of the 5G era has promoted the need for filters of different bandwidths. Thin-film bulk acoustic resonators have become the mainstream product for applications due to their excellent performance. The Keff2 of the FBAR greatly influences the bandwidth of the filter. In this paper, we designed an AlN-based adjustable Keff2 FBAR by designing parallel capacitors around the active area of the resonator. The parallel capacitance is introduced through the support column structure, which is compatible with conventional FBAR processes. The effects of different support column widths on Keff2 were verified by finite element simulation and experimental fabrication. The measured results show that the designed FBAR with support columns can achieve a Keff2 value that is 25.9% adjustable.

Effects of Purinergic Receptor Deletion or Pharmacologic Modulation on Pulmonary Inflammation in Mice.

COVID-19 disease is associated with progressive accumulation of SARS-CoV-2-specific mRNA, which is recognized by innate immune receptors, such as TLR3. This in turn leads to dysregulated production of multiple cytokines, including IL-6, IFN-γ, CXCL1, and TNF-α. Excessive production of these cytokines leads to acute lung injury (ALI), which consequently compromises alveolar exchange of O2 and CO2. It is therefore of considerable interest to develop novel therapies that reduce pulmonary inflammation and stem production of pro-inflammatory cytokines, potentially for COVID-19 patients that are at high risk of developing severe disease. Purinergic signaling has a central role in fine-tuning the innate immune system, with P2 (nucleotide) receptor antagonists and adenosine receptor agonists having anti-inflammatory effects. Accordingly, we focused here on the potential role of purinergic receptors in driving neutrophilic inflammation and cytokine production in a mouse model of pulmonary inflammation. To mimic the effects of SARS-CoV-2-specific RNA accumulation in mice, we administered progressively increasing daily doses of a viral mimetic, polyinosinic:polycytidylic acid [poly(I:C)] into the airways of mice over the course of 1 week. Some mice also received increasing daily doses of ovalbumin to mimic virus-encoded protein accumulation. Animals receiving both poly(I:C) and ovalbumin displayed particularly high cytokine levels and neutrophilia, suggestive of both innate and antigen-specific, adaptive immune responses. The extent of these responses was diminished by genetic deletion (P2Y14R, P2X7R) or pharmacologic modulation (P2Y14R antagonists, A3AR agonists) of purinergic receptors. These results suggest that pharmacologic modulation of select purinergic receptors might be therapeutically useful in treating COVID-19 and other pulmonary infections.

Real-world efficacy and safety of dolutegravir plus lamivudine versus tenofovir plus lamivudine and efavirenz in ART-naïve HIV-1-infected adults.

Limited real-world data on dolutegravir (DTG) plus lamivudine (3TC) for HIV-1-infected individuals have been reported. This study aimed to evaluated the real-world efficacy and safety of DTG + 3TC in ART-naïve HIV-1-infected adults in China. This real-world prospective observational cohort study enrolled HIV-1-infected adults receiving ART initiation with DTG + 3TC (D3 group) or tenofovir plus lamivudine and efavirenz (TDF + 3TC + EFV, TLE group) with subgroups of low viral load (LVL, ≤500,000 copies/mL) and high viral load (HVL, >500,000 copies/mL) according to baseline HIV-1 RNA. Efficacy were assessed by proportion of virologic suppression, changes of CD4+ cell count and CD4/CD8 ratio, HIV-1 DNA decay, and safety by symptoms and changes of laboratory indicators at week 4, 12, 24, 36, and 48. Totally 45 participants in D3 group and 95 in TLE group were enrolled. The proportion of HIV RNA < 50 copies/mL were 48.7% (19/39), 84.6% (33/39), 100% (39/39), 100% (39/39) in D3-LVL subgroup at week 4, 12, 24, 48, compared with 1.3% (1/75), 14.7% (11/75), 86.7% (65/75), 96.0% (72/75) in TLE-LVL subgroup, with P < .05 at week 4, 12, and 36. The proportion were 0.0% (0/6), 66.7% (4/6), 83.3% (5/6), 100% (6/6) in D3-HVL subgroup compared with 0.0% (0/20), 5.0% (1/20), 85.0% (17/20), 100% (20/20) in TLE-HVL subgroup, with P < .05 at week 12. No virologic rebound was observed in D3 group. Mean change of CD4/CD8 ratio were higher in D3-LVL versus TLE-LVL subgroup at each scheduled visit (P < .05), while CD4+ cell counts increased significantly in D3-HVL versus TLE-HVL subgroup at week 4 and 12 (P < .05). Less complaint of dizziness, insomnia, dreaminess and amnesia, lower elevated level of triglyceride and higher elevated level of creatinine from baseline to week 48 were documented in D3 group (P < .05). Total HIV-1 DNA decayed along with HIV-1 RNA after DTG + 3TC initiation in both D3-LVL and D3-HVL subgroups. DTG + 3TC achieved virological suppression more rapidly and stably versus TDF + 3TC + EFV in ART-naïve HIV-1-infected adults, with better immunological response and less adverse drug effect, and reduced total HIV-1 DNA effectively. DTG + 3TC is a potent regimen for ART-naïve individuals with HIV-1 infection.

Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy.

To increase the antitumor drug concentration in the liver tumor site and improve the therapeutic effects, a functionalized liposome (PPP-LIP) with tumor targetability and enhanced internalization after matrix metalloproteinase-2 (MMP2)-triggered cell-penetrating peptide (TATp) exposure was modified with myrcludex B (a synthetic HBV preS-derived lipopeptide endowed with compelling liver tropism) for liver tumor-specific delivery. After intravenous administration, PPP-LIP was mediated by myrcludex B to reach the hepatocyte surface. The MMP2-overexpressing tumor microenvironment deprotected PEG, exposing it to TATp, facilitating tumor penetration and subsequent efficient destruction of tumor cells. In live imaging of small animals and cellular uptake, PPP-LIP was taken up much more than typical unmodified liposomes in the ICR mouse liver and liver tumor cells. Hydroxycamptothecin (HCPT)-loaded PPP-LIP showed a better antitumor effect than commercially available HCPT injections among MTT, three-dimensional (3 D) tumor ball, and tumor-bearing nude mouse experiments. Our findings indicated that PPP-LIP nanocarriers could be a promising tumor-targeted medication delivery strategy for treating liver cancers with elevated MMP2 expression.

Structure-Activity Relationship and Neuroprotective Activity of 1,5-Dihydro-2H-naphtho[1,2-b][1,4]diazepine-2,4(3H)-diones as P2X4 Receptor Antagonists.

We analyzed the P2X4 receptor structure-activity relationship of a known antagonist 5, a 1,5-dihydro-2H-naphtho[1,2-b][1,4]diazepine-2,4(3H)-dione. Following extensive modification of the reported synthetic route, 4-pyridyl 21u (MRS4719) and 6-methyl 22c (MRS4596) analogues were most potent at human (h) P2X4R (IC50 0.503 and 1.38 µM, respectively, and selective versus hP2X1R, hP2X2/3R, hP2X3R). Thus, the naphthalene 6-, but not 7-position was amenable to substitution, and an N-phenyl ring aza-scan identified 21u with 3-fold higher activity than 5. Compounds 21u and 22c showed neuroprotective and learning- and memory-enhancing activities in a mouse middle cerebral artery occlusion (MCAO) model of ischemic stroke, with potency of 21u > 22c. 21u dose-dependently reduced infarct volume and reduced brain atrophy at 3 and 35 days post-stroke, respectively. Relevant to clinical implication, 21u also reduced ATP-induced [Ca2+]i influx in primary human monocyte-derived macrophages. This study indicates the translational potential of P2X4R antagonists for treating ischemic stroke, including in aging populations.

Recent Advances in Oral Peptide or Protein-Based Drug Liposomes.

The high physiology and low toxicity of therapeutic peptides and proteins have made them a hot spot for drug development in recent years. However, their poor oral bioavailability and unstable metabolism make their clinical application difficult. The bilayer membrane of liposomes provides protection for the drug within the compartment, and their high biocompatibility makes the drug more easily absorbed by the body. However, phospholipids-which form the membranes-are subjected to various digestive enzymes and mucosal adhesion in the digestive tract and disintegrate before absorption. Improvements in the composition of liposomes or modifying their surface can enhance the stability of the liposomes in the gastrointestinal tract. This article reviews the basic strategies for liposome preparation and surface modification that promote the oral administration of therapeutic polypeptides.

A High-Sensitivity Gravimetric Biosensor Based on S1 Mode Lamb Wave Resonator.

The development of MEMS acoustic resonators meets the increasing demand for in situ detection with a higher performance and smaller size. In this paper, a lithium niobate film-based S1 mode Lamb wave resonator (HF-LWR) for high-sensitivity gravimetric biosensing is proposed. The fabricated resonators, based on a 400-nm X-cut lithium niobate film, showed a resonance frequency over 8 GHz. Moreover, a PMMA layer was used as the mass-sensing layer, to study the performance of the biosensors based on HF-LWRs. Through optimizing the thickness of the lithium niobate film and the electrode configuration, the mass sensitivity of the biosensor could reach up to 74,000 Hz/(ng/cm2), and the maximum value of figure of merit (FOM) was 5.52 × 107, which shows great potential for pushing the performance boundaries of gravimetric-sensitive acoustic biosensors.

Stereospecific antiseizure activity in mouse and rat epilepsy models by a pyridinium inhibitor of TNFα/NFκB signaling.

Epilepsy affects over 50 million people worldwide and increases the risk of death. An intrinsic state of central inflammation, mainly driven by TNFα/NFκB signaling, may contribute to the refractory nature of some epilepsies. We have therefore hypothesized that inhibitors of this signaling pathway might be therapeutic. To test this hypothesis, we have measured the antiseizure properties of the enantiomeric compounds MRS-2481 and MRS-2485 in rodent seizure model systems. In the 6 Hz (44 mA) induced seizure test in mice, the (S) species, MRS-2485, was found to have higher protective potency and lower toxicity than the (R) species MRS-2481. However, neither of these enantiomers were protective in the MES-induced seizure test. MRS-2485 was also found to be protective in the corneal kindled mouse test. Finally, MRS-2485 reduced the post-kainate rat hippocampal slice electrical burst rate and duration. We conclude that MRS-2485, the (S)-enantiomer, is a potent inhibitor of seizure activity in mouse and rat models of epilepsy.

Dihydropyridines Potentiate ATP-Induced Currents Mediated by the Full-Length Human P2X5 Receptor.

The P2X5 receptor, an ATP-gated cation channel, is believed to be involved in tumor development, inflammatory bone loss and inflammasome activation after bacterial infection. Therefore, it is a worthwhile pharmacological target to treat the corresponding diseases, especially in minority populations that have a gene variant coding for functional homotrimeric P2X5 channels. Here, we investigated the effects of dihydropyridines on the human full-length P2X5 receptor (hP2X5FL) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage clamp method. Agonist dependency, kinetics and permeation behavior, including Cl- permeability, were similar to hP2X5FL expressed in HEK293 or 1321N1 cells. Additionally, 1,4-dihydropyridines have been shown to interact with various other purinergic receptors, and we have examined them as potential hP2X5 modulators. Of seven commercially available and four newly synthesized dihydropyridines tested at hP2X5FL, only amlodipine exerted an inhibitory effect, but only at a high concentration of 300 µM. Isradipine and-even more-nimodipine stimulated ATP-induced currents in the low micromolar range. We conclude that common dihydropyridines or four new derivatives of amlodipine are not suitable as hP2X5 antagonists, but amlodipine might serve as a lead for future synthesis to increase its affinity. Furthermore, a side effect of nimodipine therapy could be a stimulatory effect on inflammatory processes.

Bridged Piperidine Analogues of a High Affinity Naphthalene-Based P2Y14R Antagonist.

High affinity phenyl-piperidine P2Y14R antagonist 1 (PPTN) was modified with piperidine bridging moieties to probe receptor affinity and hydrophobicity. Various 2-azanorbornane, nortropane, isonortropane, isoquinuclidine, and ring-opened cyclopentylamino derivatives preserved human P2Y14R affinity (fluorescence binding assay), and their pharmacophoric overlay was compared. Enantiomeric 2-azabicyclo[2.2.1]hept-5-en-3-one precursors assured stereochemically unambiguous, diverse products. Pure (S,S,S) 2-azanorbornane enantiomer 15 (MRS4738) displayed higher affinity than 1 (3-fold higher affinity than enantiomer 16) and in vivo antihyperallodynic and antiasthmatic activity. Its double prodrug 143 (MRS4815) dramatically reduced lung inflammation in a mouse asthma model. Related lactams 21-24 and dicarboxylate 42 displayed intermediate affinity and enhanced aqueous solubility. Isoquinuclidine 34 (IC50 15.6 nM) and isonortropanol 30 (IC50 21.3 nM) had lower lipophilicity than 1. In general, rigidified piperidine derivatives did not lower lipophilicity dramatically, except those rings with multiple polar groups. P2Y14R molecular modeling based on a P2Y12R structure showed stable and persistent key interactions for compound 15.

Structure-Activity Relationship of Heterocyclic P2Y14 Receptor Antagonists: Removal of the Zwitterionic Character with Piperidine Bioisosteres.

A known zwitterionic, heterocyclic P2Y14R antagonist 3a was substituted with diverse groups on the central phenyl and terminal piperidine moieties, following a computational selection process. The most potent analogues contained an uncharged piperidine bioisostere, prescreened in silico, while an aza-scan (central phenyl ring) reduced P2Y14R affinity. Piperidine amide 11, 3-aminopropynyl 19, and 5-(hydroxymethyl)isoxazol-3-yl) 29 congeners in the triazole series maintained moderate receptor affinity. Adaption of 5-(hydroxymethyl)isoxazol-3-yl gave the most potent naphthalene-containing (32; MRS4654; IC50, 15 nM) and less active phenylamide-containing (33) scaffolds. Thus, a zwitterion was nonessential for receptor binding, and molecular docking and dynamics probed the hydroxymethylisoxazole interaction with extracellular loops. Also, amidomethyl ester prodrugs were explored to reversibly block the conserved carboxylate group to provide neutral analogues, which were cleavable by liver esterase, and in vivo efficacy demonstrated. We have, in stages, converted zwitterionic antagonists into neutral molecules designed to produce potent P2Y14R antagonists for in vivo application.

Exploration of Alternative Scaffolds for P2Y14 Receptor Antagonists Containing a Biaryl Core.

Various heteroaryl and bicyclo-aliphatic analogues of zwitterionic biaryl P2Y14 receptor (P2Y14R) antagonists were synthesized, and affinity was measured in P2Y14R-expressing Chinese hamster ovary cells by flow cytometry. Given this series' low water solubility, various polyethylene glycol derivatives of the distally binding piperidin-4-yl moiety of moderate affinity were synthesized. Rotation of previously identified 1,2,3-triazole attached to the central m-benzoic acid core (25) provided moderate affinity but not indole and benzimidazole substitution of the aryl-triazole. The corresponding P2Y14R region is predicted by homology modeling as a deep, sterically limited hydrophobic pocket, with the outward pointing piperidine moiety being the most flexible. Bicyclic-substituted piperidine ring derivatives of naphthalene antagonist 1, e.g., quinuclidine 17 (MRS4608, IC50 ≈ 20 nM at hP2Y14R/mP2Y14R), or of triazole 2, preserved affinity. Potent antagonists 1, 7a, 17, and 23 (10 mg/kg) protected in an ovalbumin/Aspergillus mouse asthma model, and PEG conjugate 12 reduced chronic pain. Thus, we expanded P2Y14R antagonist structure-activity relationship, introducing diverse physical-chemical properties.

Effects of Fermented Tea Residue on Fattening Performance, Meat Quality, Digestive Performance, Serum Antioxidant Capacity, and Intestinal Morphology in Fatteners.

This study investigated the dietary supplementation of tea residue fermented by Bacillus subtilis, Aspergillus niger, and Saccharomyces cerevisiae, to explore its effects on growth performance, digestion performance, meat quality, serum antioxidant capacity, and intestinal morphology in pigs bred for rapid growth, also known as fatteners. One hundred and ninety-two healthy "Duroc × Landrace × Yorkshire" ternary hybrid pigs (body weight 70 ± 1.0 kg) were randomly divided into four groups according to the feeding test requirements, with four replicates in each group, and 12 fatteners per replicate. The control group (CG) was fed the basal diet. Treatments 1 (T1), 2 (T2), and 3 (T3), comprising ratios of 10%, 15%, and 20% of tea residue were added to the basal diet. The test period was 60 days. The results showed that supplementation of FTR in fatteners' diets increased final body weight (FBW), average daily gain (ADG), and feed conversion ratio (FCR) in the T1 and T2 groups (p < 0.05). Compared with the other groups, the lightness (L*) and pH were significantly affected in the T2 group (p < 0.05). Compared with the CG, dietary supplementation of FTR significantly increased the nutrient digestibility of crude protein (CP), ether extract (EE), calcium (Ca), and phosphorus (P), improved the lipase and trypsin activities, and reduced drip loss and the shear force of fatteners (p < 0.05). Glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) were significantly increased in the T2 and T3 groups compared with the other groups (p < 0.05). Supplementation of FTR in the jejunum significantly increased the villi height of the T2 group and the ratio of villi height to crypt depth of the FTR groups. Compared with the other two groups, the T2 and T3 groups significantly reduced the ratio of the villous height to crypt depth in the duodenum (p < 0.05). In conclusion, the tea residue after fermentation was shown to have beneficial effects on the fattening performance, digestion performance, meat quality, serum antioxidant capacity, and intestinal morphology of fatteners.

Fluorescent 5-Pyrimidine and 8-Purine Nucleosides Modified with an N-Unsubstituted 1,2,3-Triazol-4-yl Moiety.

The Cu(I)- or Ag(I)-catalyzed cycloaddition between 8-ethynyladenine or guanine nucleosides and TMSN3 gave 8-(1- H-1,2,3-triazol-4-yl) nucleosides in good yields. On the other hand, reactions of 5-ethynyluracil or cytosine nucleosides with TMSN3 led to the chemoselective formation of triazoles via Cu(I)-catalyzed cycloaddition or vinyl azides via Ag(I)-catalyzed hydroazidation. These nucleosides with a minimalistic triazolyl modification showed excellent fluorescent properties with 8-(1- H-1,2,3-triazol-4-yl)-2'-deoxyadenosine (8-TrzdA), exhibiting a quantum yield of 44%. The 8-TrzdA 5'-triphosphate was incorporated into duplex DNA containing a one-nucleotide gap by DNA polymerase ß.