170737-46-9Relevant articles and documents
METHODS OF DETECTING NEUROLOGICAL DISORDERS VIA BINDING TO PHOSPHORYLATED TAU PROTEIN
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Page/Page column 88; 89, (2021/04/01)
Provided herein are methods and compositions for determining whether a patient suffers from a neurological disease or disorder is provided, comprising detecting the presence of a phosphorylated tau protein in a tissue of the patient, wherein the detecting comprises contacting the phosphorylated tau protein with a compound described herein.
Exploring the Effect of Aliphatic Substituents on Aryl Cyano Amides on Enhancement of Fluorescence upon Binding to Amyloid-β Aggregates
Ehrlich, Rachel S.,Shiao, Alexander L.,Li, Meihan,Teppang, Kristine L.,Jeoung, Kun Yong,Theodorakis, Emmanuel A.,Yang, Jerry
, p. 2946 - 2952 (2021/08/06)
The self-assembly of amyloid-β (Aβ) peptides into amyloid aggregates is a pathological hallmark of Alzheimer's Disease. We previously reported a fluorescent Aryl Cyano Amide (ARCAM) probe that exhibits an increase in fluorescence emission upon binding to Aβ aggregates in solution and in neuronal tissue. Here, we investigate the effect of introducing small aliphatic substituents on the spectroscopic properties of ARCAM both free in solution and when bound to aggregated Aβ. We found that introducing substituents designed to hinder the rotation of bonds between the electron donor and acceptor on these fluorophores can affect the overall brightness of fluorescence emission of the probes in amyloid-free solutions, but the relative fluorescence enhancement of these probes in amyloid-containing solutions is dependent on the location of the substituents on the ARCAM scaffold. We also observed the capability to tune the excitation or emission wavelength of these probes by introducing electron-donating or -withdrawing substituents that putatively affect either the energy required for photoexcitation or the stability of the photoexcited state. These studies reveal new design principles for developing ARCAM-based fluorescent Aβ-binding probes with an enhanced fluorescence signal compared to background and tunable spectroscopic properties, which may lead to improved chemical tools for aiding in the diagnosis of amyloid-associated neurodegenerative diseases.
COMPOSITIONS AND METHODS FOR DETECTION OF TRAUMATIC BRAIN INJURY
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, (2021/12/03)
The present disclosure relates generally to compositions and methods for determining whether a patient suffers from a traumatic brain injury (TBI) by detecting the presence of an amyloid beta protein in an eye of the patient. Also provided are compositions and methods for preparing a patient for diagnosis and treatment of traumatic brain injury (TB).
Photoactuators based on the dynamic molecular crystals of naphthalene acrylic acids driven by stereospecific [2+2] cycloaddition reactions
Liu, Jiaxi,Ye, Kaiqi,Shen, Yanbing,Peng, Jiang,Sun, Jingbo,Lu, Ran
, p. 3165 - 3175 (2020/03/19)
The photomechanical effects of the dynamic molecular crystals of halogen-substituted naphthalene acrylic acids (1FNaAA, 1ClNaAA, 1BrNaAA, 1INaAA and 6BrNaAA) have been investigated. Upon UV irradiation, the needle-like crystal of 1FNaAA curls away from the light source, while the slice-like crystal of 6BrNaAA bends towards the light source. Moreover, the light-induced bending, flipping and bursting are observed for the elongated needle-like crystals of 1FNaAA, and the slice-like crystals of 1ClNaAA and 1BrNaAA show bending, cracking, coiling, rotating and twisting triggered by 365 nm light. It is found that stereospecific [2+2] cycloaddition reactions take place in the crystals to afford one stereoisomer of β-type cyclobutanes, since 1FNaAA, 1ClNaAA, 1BrNaAA and 6BrNaAA pack in a head-to-head mode, which satisfies the Schmidt's topo-photochemical criteria. The strain can be generated and accumulated during the photodimerization, and the release of the strain leads to the photomechanical effects. This provides new clues for the development of photomechanical molecular crystals based on acrylic acids bearing halogen-substituted aromatic units.
A dicyanoisophorone-based, near-infrared, lysosome-targeting pH sensor with an extremely large Stokes shift
Cai, Chunhui,Shen, Wei,Wang, Lei,Yi, Wenjun,Yu, Shian,Zhu, Qing,Zhu, Shen
, (2020/02/27)
Intracellular pH plays an important role in various biological processes; abnormal pH changes in the intracellular compartment leads to the production of free radicals, the disruption of membrane contractility, inappropriate apoptosis, and necrosis, resulting in serious illness. Although fluorescent probes have widely been used to detect pH levels owing to their high sensitivity and specificity, there is still a demand for near-infrared (NIR) fluorescent probes with high Stokes shift. Here, a NIR fluorescent probe, PipDC, comprising N-ethyl piperazine (response unit) and naphthyl dicyanoisophorone (fluorophore), was designed for pH sensing. The probe has an extremely large Stokes shift (290 nm), and its fluorescence intensity at 730 nm sharply increases when the environment changes from basic to acidic owing to the protonation of piperazine, which results in the quenching of the photoinduced electron transfer effect. It exhibited a specific response to acidic microenvironments regardless of other interfering substances. In addition, PipDC operates well in the lysosome environment in living cells and displays an off-on fluorescence response with pH alterations. Together, these results suggest that PipDC is a promising fluorescent probe for intracellular pH sensing.
Design, synthesis, and characterization of 6-[(trimethyl)silylethynyl]naphthalene-2-ethene: A new precursor for the preparation of high-refractive-index organic materials
Hannu-Kuure, Milja,K?rkk?inen, Ari,Legrand, Sacha
, (2020/03/19)
A new polymerizable naphthalene derivative has been designed, prepared, and characterized by 1H, 13C NMR, and MS. The new monomer synthesis has successfully been accomplished from a cheap commercially available raw material, in only four steps with good yields. The four steps can be easily scaled up for manufacturing purposes. It is anticipated that the new precursor can be very useful in the preparation of valuable materials with high refractive index for numerous opto-electronic applications.
Method to discriminate amyloids using fluorescent probes
Teppang, Kristine L.,Ehrlich, Rachel S.,Yang, Jerry
, p. 91 - 114 (2020/04/28)
The aggregation of misfolded proteins into amyloids is a common characteristic of many neurodegenerative and non-neurologic diseases. Fluorescent amyloid-targeting probes that discriminate amyloids based on differences in protein composition can provide rapid information to aid in disease diagnosis. In this chapter, we present protocols for the synthesis and use of ANCA-11 as an environmentally-sensitive amyloid-targeting probe that can fluorescently discriminate between amyloids with different disease origin. We also present a protocol for preparing amyloid samples of synthetic Amyloid-β(1-42), as problems with amyloid preparations can be a large driver of time and cost for research. The methods presented here can be generalized for evaluation of other amyloid-targeting fluorescent probes with different aggregates of amyloidogenic proteins in solution or in tissue.
Comprehensive structure-activity-relationship of azaindoles as highly potent FLT3 inhibitors
Grimm, Sebastian H.,Gagestein, Berend,Keijzer, Jordi F.,Liu, Nora,Wijdeven, Ruud H.,Lenselink, Eelke B.,Tuin, Adriaan W.,van den Nieuwendijk, Adrianus M.C.H.,van Westen, Gerard J.P.,van Boeckel, Constant A.A.,Overkleeft, Herman S.,Neefjes, Jacques,van der Stelt, Mario
, p. 692 - 699 (2019/01/22)
Acute myeloid leukemia (AML) is characterized by fast progression and low survival rates, in which Fms-like tyrosine kinase 3 (FLT3) receptor mutations have been identified as a driver mutation in cancer progression in a subgroup of AML patients. Clinical trials have shown emergence of drug resistant mutants, emphasizing the ongoing need for new chemical matter to enable the treatment of this disease. Here, we present the discovery and topological structure-activity relationship (SAR) study of analogs of isoquinolinesulfonamide H-89, a well-known PKA inhibitor, as FLT3 inhibitors. Surprisingly, we found that the SAR was not consistent with the observed binding mode of H-89 in PKA. Matched molecular pair analysis resulted in the identification of highly active sub-nanomolar azaindoles as novel FLT3-inhibitors. Structure based modelling using the FLT3 crystal structure suggested an alternative, flipped binding orientation of the new inhibitors.
Enantioselective α-Benzylation of Acyclic Esters Using π-Extended Electrophiles
Schwarz, Kevin J.,Yang, Chao,Fyfe, James W. B.,Snaddon, Thomas N.
supporting information, p. 12102 - 12105 (2018/09/11)
The first asymmetric cooperative Lewis base/palladium catalyzed benzylic alkylation of acyclic esters is reported. This reaction proceeds via stereodefined C1-ammonium enolate nucleophiles. Critical to its success was the identification of benzylic phosphate electrophiles, which were uniquely reactive. Alkylated products were obtained with very high levels of enantioselectivity, and this method has been applied toward the synthesis of the thrombin inhibitor DX-9065a.
CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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, (2018/07/29)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
