succinyl norcocaine & cholera toxin B (TA-CD) / Celtic Pharma - LARVOL DELTA

Bipartite Recognition of Tail-Anchored Proteins by Sgt2 Involves both the Cytosolic and Transmembrane Domains. (PubMed, Biochemistry) - "A structural model of the Sgt2N-TACD complex supports this binding mode, and competition experiments demonstrate that Get5UBL can effectively displace TAsCD from Sgt2N via the same surface. These findings define a dual-recognition mechanism in which both the TACD and TMD contribute to Sgt2 engagement, thereby reinforcing client safeguarding and suggesting a broader role for Sgt2 in TA protein targeting."

Journal

Tangerine peel-derived nitrogen-doped carbon dots incorporated chitosan/pullulan-based active packaging film for bread packaging. (PubMed, Colloids Surf B Biointerfaces) - "Sliced bread was packaged using CS/Pul-based films and stored for 12 days at 50 % relative humidity and 25 °C to investigate changes in the quality of the bread. It was found that bread packaged with CS/Pul film integrated with N-TanCD maintained excellent bread quality relating to appearance, moisture content, hardness, weight loss, and total viable bacterial count."

Journal

Retinal Microstructural Changes Reflecting Treatment-Associated Cognitive Dysfunction in Patients with Lower-Grade Gliomas. (PubMed, Ophthalmol Sci) - "To determine whether microstructural retinal changes, tumor features, and apolipoprotein E (APOE) ε4 polymorphism are correlated with clinically detectable treatment-associated cognitive dysfunction (TACD) in patients with lower-grade gliomas...A larger study with serial eye examinations is warranted to evaluate the role of APOE ε4 and develop a predictive model. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article."

Journal • Astrocytoma • Brain Cancer • CNS Tumor • Cognitive Disorders • Glioma • Oligodendroglioma • Oncology • Ophthalmology • Solid Tumor • APOE

Online identification of potential antioxidant components and evaluation of DNA oxidative damage protection ability in Prunus persica flowers. (PubMed, Talanta) - "A high performance liquid chromatography-ultraviolet-visible detector-electrospray ionization-ion trap-time-of-flight-mass spectrometry-total antioxidant capacity determination (HPLC-UVD-ESI-IT-TOF-MS-TACD) new online technique was developed for efficient screening of potential antioxidant active components in Prunus persica flowers (PPF) from 4 origins...This also provides technical basis for rapid screening of antioxidant resources of PPF. In short, this study made the chemical composition of PPF more abundant and its potential antioxidant active compounds more explicit, which provided new ideas for the detection and development of natural antioxidants and provided scientific basis for PPF as functional food."

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Structurally Oriented Carbon Dots as ROS Nanomodulators for Dynamic Chronic Inflammation and Infection Elimination. (PubMed, ACS Nano) - "The surface C-N/C═N of CDs derived from taxus leaves (TACD) and DACD renders them with suitable band structures, facilitating absorption in the red region and efficient generation of O2·- upon light irradiation for sterilization. Specifically, the facilely prepared DACD demonstrates fascinating dynamic ROS modulating ability, making it highly suitable for addressing concurrent chronic inflammation and infection, such as diabetic wound infection. This dynamic ROS regulation strategy facilitates the realization of the precise and efficient treatment of chronic inflammation and infection with minimal side effects, holding immense potential for clinical practice."

Journal • Infectious Disease • Inflammation

Synthesis of 1,4,8-triaazacycloundecane (TACU) (ACS-Fall 2024) - "One such amine by the name of 1,5,9-triazacyclododecane (TACD) was synthesized previously due to its ability to coordinate zinc ions through its nitrogen groups by mimicking the active residues of Carboxypeptidase A. This work focuses on the synthesis of a 1,4,8-triacycloundecane (TACU) polyamine...The β-cyclodextrin ring is proposed to serve as a substrate-binding domain as well as for binding alkaline earth metal ions that will serve as Lewis acids for activating the substrate towards hydrolysis by the catalytic zinc-bound hydroxide ions in aqueous buffers. The hydrolytic function of the ligand-metal ion complex will be subsequently characterized using Michaelis-Menten enzyme kinetics."

Thermophilic-mesophilic temperature phase anaerobic co-digestion compared with single phase co-digestion of sewage sludge and food waste. (PubMed, Sci Rep) - "By adjusting the mixture ratio of sewage sludge and food waste to achieve the optimal carbon to nitrogen ratio, the effectiveness of thermophilic-mesophilic temperature phase anaerobic co-digestion (TPAcD) was evaluated in comparison to single phase mesophilic anaerobic co-digestion (MAcD) and thermophilic anaerobic co-digestion (TAcD)...Therefore, further research on TPAcD of sewage sludge and food waste is warranted due to its significant improvements in methane production rate, total methane yield, and system stability. Additionally, TPAcD contributes to reducing carbon emissions and supports the realization of "carbon neutrality"."

Journal

Synthesis and structural elucidation of a polyamine active site containing ligand mimicing carboxypeptidase A | Poster Board #818 (ACS-Sp 2024) - "The ligand of interest will be synthesized in an SN2 reaction between 1,5,9-triazacyclododecane (TACD) and mono-6-deoxy-6-(p-toluenesulfonyl)-β-cyclodextrin (TsO-β-CD) and characterized using 1H, 13C, and 1H-1H nuclear magnetic resonance and high resolution mass spectroscopy. The purified ligand will have Zn (II) and Ba (II) coordinated to the active site and hydrophobic pocket for developing the optimized conditions of Michaelis-Menten study for therapeutic inhibitors of Carboxypeptidase A."

Synthesis of an unsymmetrical polyamine mimicking the active site of carboxypeptidase A | Poster Board #2219 (ACS-Sp 2024) - "One such amine by the name of 1,5,9-Triazacyclododecane (TACD) was synthesized previously due to its ability to coordinate zinc ions through its nitrogen groups by micking the active residues of Carboxypeptidase A. This work focuses on the synthesis of a 1,5,9-triazacyclotridecane (TACT) polyamine. Once synthesized, the product will be confirmed using 1 H and 13 C nuclear magnetic resonance and mass spectroscopy before testing the effect of ring stability in Michaelis-Menten enzyme kinetics with a β-cyclodextrin covalently attached to one of the amines acting as a hydrophobic substrate pocket."

Synthesis and Isolation of Carbocation Intermediate and its uses in Drug Screening | Poster Board #799 (ACS-Sp 2024) - "Such methodologies include column chromatography development, the implementation of non-nucleophilic bases, and crystallization processes. Higher yields and purity of TACD will allow for enhanced drug screening and and medicinal applications."

Effects of mono-6-deoxy-6-(1,5,9-triazacyclododecanyl)-β-cyclodextrin catalytic hydrolysis in response to varying substrate concentration and pH | Poster Board #1042 (ACS-Sp 2024) - "This study explores the hydrolytic rate law of the Carboxypeptidase A metalloenzyme mimic, mono-6-deoxy-6-(1,5,9-triazacyclododecanyl)-β-cyclodextrin (TACD-β-CD), to quantify its dependency on substrate concentration and pH. Esterase activity of the ligand is mimicked with the coordination of Zn (II) and Ba (II) ions to allow hydrolysis of p-nitrophenyl acetate (PNPA) substrate in varying concentrations between 30-500 μM and pH 7.5-10.5. From these results, therapeutic inhibitors will be proposed to limit the hydrolysis of various natural substrates and analogs."

Synthesis and characterization of a symmetrical polyamine mimicking the active site of carboxypeptidase A | Poster Board #2223 (ACS-Sp 2024) - "Synthesis of the polyamine will be achieved using an SN2 reaction between hexahydropyrimidopyrimidine and 1,3-propandiol di-p-tosylate to form 1,5,9-triazacyclododecane (TACD). The final polyamine product will be characterized using 1 H and 13 C nuclear magnatic resonance and mass spectroscopy. Once isolated, the final product will be used as a precursor to the final β-cyclodextrin containing ligand which will be applied in Michaelis-Menten enzyme kinetics."

Framework Nucleic Acids-Based VEGF Signaling Activating System for Angiogenesis: A Dual Stimulation Strategy. (PubMed, Adv Sci (Weinh)) - "Moreover, in a diabetic mouse skin defect repair process, TACD increases blood vessel formation and collagen deposition, therefore accelerating wound healing. The novel strategy simulating VEGF and stabilizing HIF promotes blood-vessel formation in vivo and in vitro and has the potential for broad applications in the vascularization field."

Journal

Engineered anchor peptide LCI with a cobalt cofactor enhances oxidation efficiency of polystyrene microparticles. (PubMed, Angew Chem Int Ed Engl) - "The catalytically active cobalt cofactor Co-L1 or Co-L2 with a modified NNNN macrocyclic TACD ligand (TACD = 1,4,7,10-tetraazacyclododecane) is covalently bound to the anchor peptide LCI through a maleimide linker. Compared to the free cofactors, a 12- to 15-fold improvement in catalytic activity using biohybrid catalysts based on LCI_F16C was observed."

Journal

Kinetically Inert Macrocyclic Europium(III) Receptors for Phosphate. (PubMed, Inorg Chem) - "Toward that goal, four macrocyclic tris-bidentate 1,2-hydroxypyridonate (HOPO) europium(III) complexes containing either a cyclen, cyclam, TACN, or TACD ligand cap were synthesized and evaluated as phosphate receptors...Eu-cyclam-HOPO, on the other hand, is not. This study highlights the significant effect that minor changes in the ligand cap can have on both the ligand exchange rate and affinity for phosphate of tripodal 1,2-dihydroxypyridinonate complexes."

Journal • Metabolic Disorders • Nephrology • Renal Disease

Isolation of a tertiary carbocation intermediate in the synthesis of a metalloenzyme ligand (ACS-Sp 2023) - "The goal of this project is to isolate and purify the carbocation intermediate as well as increase yields of the orthoamide and, in turn, TACD. Higher yields of TACD can then be used to create ligand structures for metalloenzymes."

Synthesis of a ligand mimicking an active site of a metalloenzyme (ACS-Sp 2023) - "This presentation will describe the synthesis and characterization of one such ligand, namely, mono-6- deoxy-6-(1,5,9-triazacyclododecanyl)-cyclodextrin (TACD-β-CD) from 1,5,9- triazacyclododecane (TACD) and mono-6-deoxy-6-(p-toluenesulfonyl)-cyclodextrin (OTs-CD) to form the desired TACD-CD. The ligand is designed to have a Zn(II) and Ba(II) coordination site for cooperative catalytic hydrolysis of an activated substrate. Data from Michaelis-Menten kinetics will be presented to demonstrate substrate dependence of the catalytic reaction."

The structural mechanism for transcription activation by Caulobacter crescentus GcrA. (PubMed, Nucleic Acids Res) - "We determined two cryo-EM structures of C. crescentus GcrA-bound transcription activation complexes, GcrA TACU and GcrA TACD, which comprise GcrA, RNAP, σ70 and promoter DNA with GcrA cis elements at either the upstream or downstream of TSS at 3.6 and 3.8 Å, respectively...Our results suggest that GcrA likely forms a functionally specialized GcrA-RNAP-σA holoenzyme, in which GcrA first locates its cis element and then facilitates RNAP to load on core promoter at its proximal region. The sequence-specific interaction of GcrA and DNA is disrupted either at the stage of RPo formation or promoter escape depending on the location of GcrA cis elements relative to TSS."

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Calcium Hydride Cation Dimer Catalyzed Hydrogenation of Unactivated 1-alkenes and H2 Isotope Exchange: Competitive Ca-H-Ca Bridges and Terminal Ca-H Bonds. (PubMed, Chemistry) - "Recently, it was shown that the double Ca-H-Ca bridged calcium hydride cation dimer complex [LCaH 2 CaL] 2+ (macrocyclic ligand L = NNNN-tetradentate Me 4 TACD) showed remarkable activity in catalyzing the hydrogenation of unactivated 1-alkenes as well as the H 2 isotope exchange under mild conditions, tentatively via terminal Ca-H bond of cation monomer LCaH + . In this DFT mechanistic work, a novel substrate-dependent catalytic mechanism is disclosed involving cooperative Ca-H-Ca bridges for H 2 isotope exchange, competitive Ca-H-Ca bridges and terminal Ca-H bonds for anti-Markovnikov addition of unactivated 1-alkenes, and terminal Ca-H bonds for Markovnikov addition of conjugation-activated styrene. THF-coordination plays a key role in favoring the anti-Markovnikov addition while strong cation-π interactions direct the Markovnikov addition to terminal Ca-H bonds."

Journal

Formation and Reactivity of a Hexahydridosilicate [SiH6]2- Coordinated by a Macrocycle-Supported Strontium Cation. (PubMed, Angew Chem Int Ed Engl) - "The reaction of a 1:2 mixture of cationic benzyl complex and neutral dibenzyl with phenylsilane gave the trinuclear silanide complex [(Me 4 TACD) 3 Sr 3 (µ 2 -H) 3 (µ 3 -SiH 3 )][A]. In contrast, n OctSiH 3 led to the trinuclear complex with an (n-alkyl)pentahydridosilicate [(Me 4 TACD) 3 Sr 3 (µ 2 -H) 3 (µ 3 -SiH 5 n Oct)][A]."

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Impact of needle positioning on ablation success of irreversible electroporation: a unicentric retrospective analysis. (PubMed, Sci Rep) - "As most important geometrical parameter TACD could be identified. Main reasons for high TACD were insufficient needle depth and a lesion location out of the needle plane."

Journal • Retrospective data • Oncology • MRI

Calcium Hydride Catalysts for Olefin Hydrofunctionalization: Ring Size Effect of Macrocyclic Ligands on Activity. (PubMed, Chemistry) - "The calcium hydride catalyzed the hydrogenation and hydrosilylation of unactivated olefins faster than the analogous calcium complex stabilized by the twelve-membered NNNN macrocycle Me 4 TACD (Me 4 TACD = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane). Kinetic investigations indicate that higher catalytic efficiency for the Me 5 PACP stabilized calcium hydride is due to easier dissociation of the dimer in solution when compared to the Me 4 TACD analogue."

Journal

Treosulfan based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicentre experience. (PubMed) - Blood - "Treosulfan containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome particularly on fertility."

Journal • Retrospective data • Biosimilar • Complement-mediated Rare Disorders • Graft versus Host Disease • Immunology

Thioredoxin (Trx1) regulates CD4 membrane domain localization and is required for efficient CD4-dependent HIV-1 entry. (PubMed) - "Extracellular redox conditions may regulate CD4 function by potentiating changes in its membrane domain localization."

Journal • Biosimilar • Gene Therapies

Mononuclear Alkali Metal Organoperoxides Stabilized by an NNNN-Macrocycle and Short Hydrogen Bonds from ROOH Molecules. (PubMed, Chemistry) - "A series of light alkali metal organoperoxides [MOOR] (M = Li, Na, K; R = tBu, CMe2Ph) were isolated in mononuclear form, aided by the tetradentate and neutral NNNN-type macrocycle Me4TACD (L; Me4[12]aneN4 = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane) and strong hydrogen bonds from additional ROOH molecules. The Na and K compounds are characterized by short OH···O contacts, in the case of the Na derivative as short as 2.41 Å."

Journal • Biosimilar