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Chembiochem : a European Journal of... Aug 2016Development of new fluorescent peptide nucleic acids (PNAs) is important for fundamental research and practical applications. The goal of this study was the design of...
Development of new fluorescent peptide nucleic acids (PNAs) is important for fundamental research and practical applications. The goal of this study was the design of fluorogenic nucleobases for incorporation in triplex-forming PNAs. The underlying design principle was the use of a protonation event that accompanied binding of a 2-aminopyridine (M) nucleobase to a G-C base pair as an on switch for a fluorescence signal. Two fluorogenic nucleobases, 3-(1-phenylethynyl)-M and phenylpyrrolo-M, were designed, synthesized and studied. The new M derivatives provided modest enhancement of fluorescence upon protonation but showed reduced RNA binding affinity and quenching of fluorescence signal upon triple-helix formation with cognate double-stranded RNA. Our study illustrates the principal challenges of design and provides guidelines for future improvement of fluorogenic PNA nucleobases. The 3-(1-phenylethynyl)-M may be used as a fluorescent nucleobase to study PNA-RNA triple-helix formation.
Topics: Aminopyridines; Fluorescence; Molecular Structure; Peptide Nucleic Acids
PubMed: 27223320
DOI: 10.1002/cbic.201600182 -
Anesthesiology May 1979To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant...
To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism, while 0.5 mg/kg produced a mean 24 +/- 6 per cent (peak) antagonism. The dose that produced 50 per cent antagonism (ED50) of neostigmine alone was 22 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 micrograms/kg. The ED50 of pyridostigmine alone was 110 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 micrograms/kg. 4-Aminopyridine prolonged the onset times of both neostigmine and pyridostigmine, but prolonged the duration of action of neostigmine only. At a given level of antagonism of pancuronium, adding 4-aminopyridine 0.35 mg/kg, to neostigmine and to pyridostigmine decreased the amounts of atropine needed to prevent a change in heart rate by 68 and 70 per cent, respectively. The authors conclude that 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Also, less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.
Topics: Adult; Aminopyridines; Atropine; Dose-Response Relationship, Drug; Drug Synergism; Heart Rate; Humans; Muscle Relaxation; Neostigmine; Neuromuscular Junction; Pancuronium; Pyridostigmine Bromide
PubMed: 453559
DOI: 10.1097/00000542-197905000-00008 -
Chemistry, An Asian Journal Jul 2013Pyrrole victory: Cyclopenta[b]pyrroles have been synthesized by the rhodium(III)-catalyzed oxidative annulative coupling of 1,2-diketones, 2-aminopyridine, and alkynes....
Pyrrole victory: Cyclopenta[b]pyrroles have been synthesized by the rhodium(III)-catalyzed oxidative annulative coupling of 1,2-diketones, 2-aminopyridine, and alkynes. This transformation can also be carried out in a one-pot sequence, thereby providing a quick and straightforward access to synthetically and pharmaceutically important cyclopenta[b]pyrroles.
Topics: Alkynes; Aminopyridines; Catalysis; Cyclization; Ketones; Oxidation-Reduction; Pyrroles; Rhodium; Stereoisomerism
PubMed: 23666799
DOI: 10.1002/asia.201300341 -
Biomedical Chromatography : BMC Nov 2020This study aimed to develop an analytical method to determine the quantity of the impurity 3-aminopyridine (3AP). 3-Aminopyridine is a reactive reagent in the synthesis...
This study aimed to develop an analytical method to determine the quantity of the impurity 3-aminopyridine (3AP). 3-Aminopyridine is a reactive reagent in the synthesis of linagliptin. The method was sensitive at level of 30.0 ppm of 3AP relative to linagliptin. The analysis was carried out using hydrophilic interaction liquid chromatography. The analytical column was Tracer Extrasil Silica (150 × 4.0 mm, 3 μm). A mobile phase of water-acetonitrile (10:90, v/v) containing 10.0 mM ammonium acetate was prepared and adjusted to pH 6.0. A UV detector was used to detect the amount of 3AP at a wavelength of 298 nm. Validation of the method was performed as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use in terms of detection limit, quantitation limit, linearity, accuracy, precision, specificity and robustness. The calibration curve was linear (r = 0.999) for 3AP concentration in the range of 30.0-450.0 ppm. This method showed a good sensitivity with a detection limit and a quantitation limit of 7.5 and 25.0 ppm, respectively.
Topics: Aminopyridines; Chromatography, High Pressure Liquid; Drug Contamination; Hydrophobic and Hydrophilic Interactions; Limit of Detection; Linagliptin; Linear Models; Mutagens; Reproducibility of Results; Spectrophotometry, Ultraviolet
PubMed: 32579716
DOI: 10.1002/bmc.4930 -
Biophysical Journal Jun 1986A single-channel recording of the transient outward current (A-current) was obtained from dorsal root ganglion cells in culture using patch-clamp techniques....
A single-channel recording of the transient outward current (A-current) was obtained from dorsal root ganglion cells in culture using patch-clamp techniques. Depolarization of the membrane patch elicited pulse like current of a uniform amplitude in an outward direction, of which the unitary conductance was 20 pS. Alteration of extracellular ionic compositions indicated that the charge carriers were K ions. A systematic study was made on the voltage-dependence of the ensemble average current; (a) the activation started at a potential around -60 mV; (b) the time course of the activation was relatively rapid; (c) the channel was completely inactivated at a potential positive to -40 mV. Two time constants (tau f = 100 ms and tau s = 4,000 ms) were detected in the decay of the current indicating that the channels had two different states of inactivation. A convulsant, 4-aminopyridine (4-AP), acted on the channel only from the intracellular side of the membrane. 4-AP (5 mM) reduced not only mean open time (by 50%) but also the single-channel conductance (by 20%). The properties of the channel were independent of Ca ions in the intracellular space.
Topics: 4-Aminopyridine; Aminopyridines; Animals; Electric Stimulation; Ganglia, Spinal; Guinea Pigs; Ion Channels; Kinetics; Membrane Potentials; Neurons, Afferent; Potassium
PubMed: 2424519
DOI: 10.1016/S0006-3495(86)83754-7 -
Journal of the Autonomic Nervous System Sep 1984Sympathetic preganglionic neuron (SPN) activity (mass or single unit discharge) was recorded extracellularly from axons of the cervical sympathetic trunk (CST) in...
Sympathetic preganglionic neuron (SPN) activity (mass or single unit discharge) was recorded extracellularly from axons of the cervical sympathetic trunk (CST) in unanaesthetized, midcollicular decerebrate or C1 spinal anemically decerebrate cats which were paralyzed and artificially ventilated. Phrenic motoneuron activity was also recorded in the midcollicular preparation. The drug 4-aminopyridine (4-AP) was administered intravenously. Doses of 0.5 to 1.0 mg/kg increased the background firing rate of SPNs in a dose-dependent manner. These doses increased the repetition rate of phrenic nerve bursts and, in a parallel fashion, that of the inspiration-synchronous activity of the CST. In contrast, the action of 4-AP on activity evoked by stimulation of high threshold myelinated afferents in the radial, femoral or pelvic nerve, or in the L7 dorsal root, was very variable. The evoked responses could be increased, decreased or not affected by the drug. Thus, treatment with 4-AP produces a graded increase in background firing of SPNs, but the drug is ineffective at reliably enhancing somato- or viscero-sympathetic reflexes.
Topics: 4-Aminopyridine; Aminopyridines; Animals; Cats; Decerebrate State; Dose-Response Relationship, Drug; Electric Stimulation; Ganglia, Sympathetic; Neurons; Phrenic Nerve; Reflex; Reflex, Monosynaptic; Respiration; Sympathetic Nervous System
PubMed: 6491160
DOI: 10.1016/0165-1838(84)90077-8 -
Angewandte Chemie (International Ed. in... Apr 2017Hydrogen atoms play a key role in protein-ligand recognition. They determine the quality of established H-bonding networks and define the protonation of bound ligands....
Hydrogen atoms play a key role in protein-ligand recognition. They determine the quality of established H-bonding networks and define the protonation of bound ligands. Structural visualization of H atoms by X-ray crystallography is rarely possible. We used neutron diffraction to determine the positions of the hydrogen atoms in the ligands aniline and 2-aminopyridine bound to the archetypical serine protease trypsin. The resulting structures show the best resolution so far achieved for proteins larger than 100 residues and allow an accurate description of the protonation states and interactions with nearby water molecules. Despite its low pK of 4.6 and a large distance of 3.6 Å to the charged Asp189 at the bottom of the S1 pocket, the amino group of aniline becomes protonated, whereas in 2-aminopyridine, the pyridine nitrogen picks up the proton although its amino group is 1.6 Å closer to Asp189. Therefore, apart from charge-charge distances, tautomer stability is decisive for the resulting binding poses, an aspect that is pivotal for predicting correct binding.
Topics: Aminopyridines; Aniline Compounds; Drug Discovery; Humans; Hydrogen Bonding; Ligands; Models, Molecular; Neutron Diffraction; Protons; Trypsin; Trypsin Inhibitors
PubMed: 28371253
DOI: 10.1002/anie.201701038 -
Advances in Nutrition (Bethesda, Md.) May 2012Human milk and colostrum contain ∼12-13 g/L and ∼22-24 g/L of oligosaccharides, respectively. The chemical structures of >100 human milk oligosaccharides (HMO) have...
Human milk and colostrum contain ∼12-13 g/L and ∼22-24 g/L of oligosaccharides, respectively. The chemical structures of >100 human milk oligosaccharides (HMO) have been characterized to date. We determined the concentrations of 10 neutral and 9 acidic colostrum HMO collected during the first 3 d of lactation by using reverse phase HPLC after derivatization with 2-aminopyridine or 1-methyl-3-phenyl-5-pyrazolon. The predominant oligosaccharides were Fuc(α1-2)Gal(β1-4Glc (2'-FL), Fuc(α1-2)Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc (LNFP I), Fuc(α1-2)Gal(β1-3)[Fuc(α1-4)]GlcNAc(β1-3)Gal(β1-4)Glc (LNDFH I), and Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc (LNT), the concentration of each of which was ∼1-3 g/L. Because these HMO, other than 2'-FL, all contain the Lacto-N-biose type I structure [Gal(β1-3)GlcNAc], we conclude that HMO containing the type I structure predominate over those containing the N-acetyllactosamine type II structure [Gal(β1-4)GlcNAc]. This appears to be a feature that is specific to humans, because the milk and colostrum of other species, including apes and monkeys, either contain only type II oligosaccharides or type II predominate over type I. It is possible that type I HMO may have importance as substrates for beneficial bifidobacteria in breast-fed infants. The biological importance of type I HMO predominance warrants further study, both in relation to human health and to human evolution.
Topics: Aminopyridines; Animals; Antipyrine; Chromatography, High Pressure Liquid; Colostrum; Edaravone; Female; Humans; Infant; Lactation; Metagenome; Milk, Human; Oligosaccharides; Primates
PubMed: 22585927
DOI: 10.3945/an.111.001412 -
Journal of Biomolecular Structure &... Nov 2023DeThe adsorption of 2-aminopyridine (2-AP) and 3-aminopyridine (3-AP) on the external surface of BN and AlN fullerene-like nanocages (FLNs) is probed herein via...
DeThe adsorption of 2-aminopyridine (2-AP) and 3-aminopyridine (3-AP) on the external surface of BN and AlN fullerene-like nanocages (FLNs) is probed herein via DFT/M06-2X/6-311G(d,p) level of theory. It came out from the study that all FLN@X-AP states investigated are spontaneously formed. Moreover, topological analysis demonstrated that the boron nitride FLN can strongly adsorbed the APs through B-N covalent interactions. A significant change in the HOMO-LUMO band gap of BN, with values of 22.01 and 32.71% have been obtained following the adsorption of 2-AP and 3-AP respectively. Accordingly, the conductivity of BN is greatly enhanced by the adsorption of the APs. The above mentioned observations, combined with those found from the analysis of dipole moments and molecular electrostatic potential maps predict BN to be more sensitive to the aminopyridines investigated than the AlN FLN from the theoretical point of view.Communicated by Ramaswamy H. Sarma.
Topics: Fullerenes; Density Functional Theory; Aminopyridines
PubMed: 36379673
DOI: 10.1080/07391102.2022.2146199 -
Toxicon : Official Journal of the... 1987Clostridium botulinum neurotoxins inhibit acetylcholine release at neuromuscular junctions. Agents stimulating neurotransmitter efflux, such as 3,4-diaminopyridine...
Clostridium botulinum neurotoxins inhibit acetylcholine release at neuromuscular junctions. Agents stimulating neurotransmitter efflux, such as 3,4-diaminopyridine (3,4-DAP), could be useful for botulism therapy. Treatment with 3,4-DAP (8 mg/kg hourly, beginning 3 hr after toxin injection) failed to increase the survival times of mice receiving 10, 20 or 40 LD50 type C, but did prolong the survival of those receiving 20 LD50 type A. This difference in 3,4-DAP efficacy may reflect variations in the molecular mechanism of action of types A and C botulinum neurotoxins.
Topics: 4-Aminopyridine; Acetylcholine; Amifampridine; Aminopyridines; Animals; Botulism; Mice; Neuromuscular Junction
PubMed: 3433299
DOI: 10.1016/0041-0101(87)90166-8