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NNMTiyog ib qho kev sib xyaw ua ke ntawm ntau cov amino acids txuas nrog peptide bonds, CAS 42464-96-0.5-amino-1 mqyog ib qho kev sib xyaw ua ke ntawm ntau cov amino acids txuas nrog peptide bonds, thiab nws cov qauv thiab cov qauv yuav txawv nyob ntawm seb hom thiab kev sib txuas ntawm cov amino acids. Cov amino acids hauv NNMT feem ntau suav nrog aspartic acid, alanine, thiab glycine, uas tsim cov chains polypeptide los ntawm peptide bonds. Hauv cov saw peptide, pawg R ntawm txhua cov amino acid yuav muaj cov tshuaj sib txawv, uas ua rau peptide NNMT muaj ntau hom tshuaj thiab cov khoom siv. Cov kua qaub-peptide ntawm peptide NNMT feem ntau cuam tshuam los ntawm cov kua qaub-piv txwv ntawm nws cov amino acids thiab cov qauv peptide daim ntawv cog lus. Vim muaj cov tshuaj sib txawv ntawm R pawg uas tsim cov amino acids, cov kua qaub-peptide NNMT kuj sib txawv nyob ntawm hom thiab txoj kev sib txuas ntawm cov amino acids. Feem ntau, peptide NNMT muaj cov kua qaub qis dua -cov khoom siv hauv paus, tab sis tseem muaj qee cov kua qaub- cov tshuaj tiv thaiv kab mob. Lub redox zog ntawm peptide NNMT feem ntau cuam tshuam los ntawm cov khoom redox ntawm cov amino acids thiab cov qauv peptide daim ntawv cog lus. Vim yog cov nyiaj tsis txaus ntseeg hauv R pawg thiab peptide daim ntawv cog lus uas tsim cov amino acids, peptide NNMT nthuav tawm qee yam kev ua haujlwm redox. Feem ntau, peptide NNMT muaj qis redox zog, tab sis nyob rau hauv tej yam kev mob, nws cov tshuaj tiv thaiv redox tej zaum yuav txhim kho.
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Optical zog ntawm peptideNNMTiFeem ntau cuam tshuam los ntawm cov khoom siv kho qhov muag ntawm cov amino acids thiab cov qauv peptide daim ntawv cog lus. Vim yog kev ua haujlwm kho qhov muag ntawm R pawg thiab peptide daim ntawv cog lus uas tsim cov amino acids, peptide 5-Amino-1-methylquinolinium kuj muaj cov haujlwm kho qhov muag. Feem ntau, cov khoom kho qhov muag ntawm peptide 5-Amino-1-methylquinolinium zoo ib yam li cov amino acids, tab sis nyob rau hauv qee yam kev mob, nws cov khoom kho qhov muag yuav hloov.
Lub complexation zog ntawm peptide 5-Amino-1-methylquinolinium yog feem ntau cuam tshuam los ntawm cov complexation ntawm cov amino acids thiab cov peptide daim ntawv cog lus. Vim muaj cov pab pawg sib koom ua ke hauv R pawg thiab peptide daim ntawv cog lus uas tsim cov amino acids, peptide 5-Amino-1-methylquinolinium muaj qee yam muaj peev xwm chelating. Feem ntau, peptide 5-Amino-1-methylquinolinium tuaj yeem tsim cov complexes nrog qee cov hlau ions, tab sis nws cov khoom chelating muaj feem xyuam rau cov amino acid tshwj xeeb muaj pes tsawg leeg thiab cov qauv ntawm pawg chelating.
Cov khoom decomposition ntawm peptide 5-Amino-1-methylquinolinium feem ntau cuam tshuam los ntawm cov khoom tawg ntawm cov amino acids thiab cov qauv peptide daim ntawv cog lus. Vim qhov tsis ruaj khov ntawm R pawg thiab peptide daim ntawv cog lus uas tsim cov amino acids, peptide 5-Amino-1-methylquinolinium tuaj yeem raug decomposition nyob rau hauv qee yam mob. Feem ntau, peptide 5-Amino-1-methylquinolinium yog nquag decomposition nyob rau hauv qhov kub thiab txias, muaj zog acid los yog muaj zog puag tej yam kev mob, tab sis nyob rau hauv tej yam kev mob, nws decomposition cov tshuaj tiv thaiv tej zaum yuav inhibited los yog txhawb.
Nws tau pom cov kev cia siab dav dav hauv thaj chaw xws li kev tshawb fawb tshuaj thiab kev tsim kho, kev tshawb fawb biochemical, cov ntaub ntawv tshawb fawb, thiab cov tshuaj tiv thaiv catalytic. Raws li NNMT inhibitor, nws lub peev xwm hauv kev kho mob rog thiab rov tsim cov leeg nqaij yog qhov tshwj xeeb; Raws li kev sojntsuam fluorescent thiab catalytic ligand, nws cov nqi tsis tuaj yeem tsis quav ntsej.
1. Raws li nicotinamide N-methyltransferase inhibitor
NNMT yog ib qho tseem ceeb enzyme koom nrog hauv nicotinamide metabolism, thiab nws overexpression yog ze ze rau cov kab mob xws li rog rog, metabolic syndrome, thiab muscular atrophy. 5-amino-1-methylquinoline-1-ium iodide, raws li ib tug npaum me me molecule inhibitor, muaj peev xwm xaiv khi rau NNMT cov kev ua ub no tseem ceeb (substrate) ₅₀=1.2 μ M). Cov yam ntxwv no ua rau nws muaj txiaj ntsig zoo hauv kev kho cov kab mob metabolic:
Kev Noj Qab Haus Huv Kev Noj Qab Haus Huv: Hauv kev noj zaub mov kom rog rog tus qauv, 5-Amino-1-methylquinolinium ua ke nrog kev hloov pauv kev noj haus tuaj yeem ua kom hnyav thiab rog, nce qhov sib piv ntawm lean lub cev hnyav rau tag nrho lub cev qhov hnyav, txo qhov hnyav ntawm cov nqaij dawb adipose hauv daim siab thiab epididymis, thiab txhim kho daim siab steatosis.
Nws cov txheej txheem ntawm kev ua haujlwm yog cuam tshuam nrog kev tswj hwm cov yam ntxwv metabolomics ntawm cov ntaub so ntswg adipose, uas tuaj yeem ua rau kom muaj ntau ntawm ketogenic amino acids thiab hloov cov qib ntawm lub zog metabolism cuam tshuam nrog cov metabolites.
Kev tsim cov leeg nqaij: 5-Amino-1-methylquinolinium tuaj yeem txhawb kev sib txawv ntawm cov leeg nqaij hauv vitro, txhim khu kev sib xyaw thiab kev tsim muaj peev xwm ntawm cov leeg leeg hauv cov nas laus. Hauv cov qauv kev raug mob ntawm cov leeg nqaij, kev txhaj tshuaj subcutaneous ntawm 5-Amino-1-methylquinolinium (5 mg / kg thiab 10 mg / kg) tuaj yeem ua rau nce qhov feem pua ntawm cov leeg pob txha / cov leeg hlwb los ntawm 60% thiab 75%, feem, thiab nce qhov feem pua ntawm cov leeg nqaij nuclei. Tsis tas li ntawd, qhov sib xyaw ua ke tau pom tias muaj kev ua siab ntev rau cov nas laus thiab tsis muaj kev cuam tshuam rau lub cev lossis kev coj cwj pwm txawv txawv.
2. Ua ib qho nruab nrab hauv kev sib xyaw tshuaj
Cov qauv quinoline thiab cov pab pawg ua haujlwm amino ntawm 5-Amino-1-methylquinolinium ua rau nws yog ib qho tseem ceeb hauv nruab nrab ntawm cov tshuaj chemical synthesis. Nws cov derivatives lossis cov qauv uas muaj nitrogen feem ntau yog siv los tsim cov tshuaj tua kab mob, tshuaj tua kab mob, thiab tshuaj tiv thaiv qog. Piv txwv li, cov tebchaw nrog cov kev ua ub no tshwj xeeb tuaj yeem tau txais los ntawm kev hloov kho cov qauv, uas tuaj yeem tsom cov kab mob tshwj xeeb thiab muab lub hauv paus rau kev tsim cov tshuaj tshiab.
Cov ntawv thov hauv kev tshawb fawb biochemistry
1. Fluorescent probes thiab cov cim
Quinoline tebchaw yog dav siv los ua fluorescent sojntsuam nyob rau hauv biochemical thiab molecular biology tshawb fawb vim lawv muaj zog fluorescence zog . 5-Amino-1-methylquinolinium yuav siv tau raws li ib tug fluorescent marker rau:
Cell imaging: Kev pom ntawm cov qauv tshwj xeeb lossis cov molecules hauv cov hlwb los ntawm kev khi tshwj xeeb rau lub hom phiaj molecules.
Molecular sensing: kuaj xyuas qhov concentration ntawm biomolecules lossis ib puag ncig kev hloov pauv (xws li pH, ion zog, thiab lwm yam).
Kev tshawb fawb txog kev sib cuam tshuam ntawm cov protein: Kev txheeb xyuas qhov kev hloov pauv ntawm cov protein-protein lossis protein ligand kev sib cuam tshuam.
2. Kev tshawb fawb txog metabolic
Hauv kev tshawb fawb txog kev rog thiab cov nqaij ntshiv, 5-Amino-1-methylquinolinium kev kho mob tuaj yeem ua rau muaj kev hloov pauv tseem ceeb hauv cov yam ntxwv metabolomic ntawm cov ntaub so ntswg adipose. Piv txwv li, hauv cov qauv nas rog rog, qhov sib xyaw ua ke tuaj yeem ua rau muaj ntau ntawm ketogenic amino acids thiab hloov cov theem ntawm cov metabolites ntsig txog lub zog metabolism. Cov kev tshawb pom no muab pov thawj metabolic rau kev nkag siab txog cov txheej txheem ntawm kev ua ntawm 5-Amino-1-methylquinolinium thiab kev tshawb fawb hauv paus rau nws daim ntawv thov kev kho mob.
Cov ntawv thov hauv cov ntaub ntawv tshawb fawb
1. Cov khoom siv hluav taws xob organic
NNMTitau qhia txog qhov muaj txiaj ntsig zoo hauv kev tshawb fawb ntawm cov khoom siv hluav taws xob organic, tshwj xeeb tshaj yog nyob rau hauv thaj chaw ntawm cov organic teeb pom kev zoo -emitting diodes (OLEDs) thiab hnub ci hlwb:
OLEDs: Lawv cov qauv hluav taws xob tshwj xeeb tuaj yeem muab cov khoom siv nrog cov khoom siv luminescent zoo, xws li fluorescence quantum yield thiab adjustable emission wavelength.
Hnub ci hlwb: Raws li cov duab hluav taws xob lossis cov khoom siv hluav taws xob thauj khoom, 5-Amino-1-methylquinolinium tuaj yeem txhim kho lub teeb pom kev zoo thiab them nyiaj sib cais, yog li txhim kho cov cuab yeej ua haujlwm.
2. Catalytic cov tshuaj tiv thaiv ligand
Hauv kev hloov pauv hlau catalytic cov tshuaj tiv thaiv, 5-Amino-1-methylquinolinium tuaj yeem ua raws li ligand los tsim kev sib koom ua ke nrog cov chaw hlau hlau, txhim kho catalytic efficiency. Piv txwv li:
Redox cov tshuaj tiv thaiv: Txhawb cov tshuaj tiv thaiv los ntawm stabilizing cov hlau active chaw los yog kho cov electron tis.
Asymmetric catalysis: Raws li ib tug chiral ligand, nws induces khoom stereoselectivity thiab txhim kho synthesis efficiency.
Daim ntawv thov nyob rau hauv lub tshav pob ntawm cov tshuaj tiv thaiv catalytic
1. Organic synthesis catalysis
5-Amino-1-methylquinolinium tuaj yeem siv los ua catalyst lossis catalyst precursor hauv organic synthesis, koom nrog ntau hom tshuaj tiv thaiv:
C-N daim ntawv cog lus: Tsim cov nitrogen- muaj cov tshuaj heterocyclic los ntawm cov tshuaj catalytic amination lossis cov tshuaj tiv thaiv amination.
Oxidation cov tshuaj tiv thaiv: Raws li oxidation catalyst, nws ua tiav kev hloov pauv ntawm cawv rau aldehydes lossis ketones.
2. Daim ntawv thov ntawm photocatalysis
Raws li nws cov khoom fluorescence, 5-Amino-1-methylquinolinium tuaj yeem ua lub luag haujlwm hauv cov tshuaj tiv thaiv photocatalytic, xws li:
Lub teeb uas tau tsav cov organic synthesis: Siv lub teeb lub zog los txhawb cov catalysts thiab tsav cov kev hloov pauv ntawm qhov nyuaj rau kev ua haujlwm.
Kev kho ib puag ncig: Degradation ntawm cov organic pollutants los yog txo cov hlau hnyav ions.
Cov txheej txheem tshuaj synthesis ntawm peptideNNMTifeem ntau yog siv cov txheej txheem Solid Phase Peptide Synthesis (SPPS).
Cov txheej txheem tshuaj synthesis ntawm peptide NNMT yog raws li hauv qab no:
Txuas cov amino acid residues uas yuav tsum tau mus rau cov resin kom raug los tsim cov amino resin. Hauv cov kauj ruam no, kev saib xyuas yuav tsum tau them rau qhov tseeb ntawm cov amino acid residues thiab xaiv cov pab pawg tiv thaiv.
Sib tov cov amino resin nrog qhov xav tau condensation reagent thiab hnov mob ntawm qhov kub thiab txias thiab lub sijhawm los tsim peptide bonds. Nyob rau hauv cov kauj ruam no, nws yog ib qho tsim nyog yuav tau them sai sai rau tus nqi ntawm cov condensation reagents thiab cov kev mob tshwm sim los xyuas kom meej qhov ua tau zoo ntawm peptide daim ntawv cog lus thiab qhov zoo ntawm cov khoom.
Cov khoom siv tshuaj tiv thaiv yog kho nrog cov tshuaj tiv thaiv kom tshem tawm cov pab pawg tiv thaiv ntawm cov amino acid residues. Hauv cov kauj ruam no, nws yog ib qho tsim nyog yuav tsum tau them sai sai rau hom thiab ntau npaum li cas ntawm tus neeg saib xyuas kev tiv thaiv, nrog rau cov tshuaj tiv thaiv, kom ntseeg tau tias kev ua haujlwm ntawm kev tiv thaiv thiab qhov zoo ntawm cov khoom.
Hloov cov khoom uas tsis muaj kev tiv thaiv nrog cov kuab tshuaj uas tsim nyog kom tshem tawm cov khoom siv tsis zoo thiab cov impurities. Hauv cov kauj ruam no, nws yog ib qho tsim nyog yuav tsum tau them sai sai rau hom thiab qhov hnyav, nrog rau cov kev hloov pauv, kom ntseeg tau tias cov khoom zoo thiab cov txiaj ntsig ntawm cov khoom.
Kev ua kom huv thiab kev txheeb xyuas cov khoom txav mus los, suav nrog recrystallization, chromatographic tsom xam, kev tsom xam spectrometry, thiab lwm yam. Nyob rau hauv cov kauj ruam no, yuav tsum tau them nyiaj mloog mus rau kev xaiv ntawm purification thiab kev txheeb xyuas cov txheej txheem thiab kev tswj xyuas kom ntseeg tau tias purity thiab zoo ntawm cov khoom raws li cov kev cai.
Nyob rau hauv cov txheej txheem tshuaj synthesis ntawm peptideNNMTi, cov ntsiab lus hauv qab no yuav tsum tau sau tseg:
Cov khoom kho qhov muag ntawm peptide NNMT feem ntau cuam tshuam los ntawm cov khoom siv kho qhov muag ntawm cov amino acids thiab cov qauv peptide daim ntawv cog lus. Vim yog kev ua haujlwm kho qhov muag ntawm R pawg thiab peptide daim ntawv cog lus uas tsim cov amino acids, peptide 5-Amino-1-methylquinolinium kuj muaj cov haujlwm kho qhov muag. Feem ntau, cov khoom kho qhov muag ntawm peptide 5-Amino-1-methylquinolinium zoo ib yam li cov amino acids, tab sis nyob rau hauv qee yam kev mob, nws cov khoom kho qhov muag yuav hloov.
Lub complexation zog ntawm peptide NNMT yog feem ntau cuam tshuam los ntawm complexation zog ntawm cov amino acids thiab cov peptide daim ntawv cog lus qauv. Vim muaj cov pab pawg sib koom ua ke hauv R pawg thiab peptide daim ntawv cog lus uas tsim cov amino acids, peptide 5-Amino-1-methylquinolinium muaj qee yam muaj peev xwm chelating. Feem ntau, peptide 5-Amino-1-methylquinolinium tuaj yeem tsim cov complexes nrog qee cov hlau ions, tab sis nws cov khoom chelating muaj feem xyuam rau cov amino acid tshwj xeeb muaj pes tsawg leeg thiab cov qauv ntawm pawg chelating.
Cov khoom decomposition ntawm peptide NNMT feem ntau cuam tshuam los ntawm cov khoom decomposition ntawm cov amino acids thiab cov qauv peptide bond. Vim qhov tsis ruaj khov ntawm R pawg thiab peptide daim ntawv cog lus uas tsim cov amino acids, peptide 5-Amino-1-methylquinolinium tuaj yeem raug decomposition nyob rau hauv qee yam mob. Feem ntau, peptide 5-Amino-1-methylquinolinium yog nquag decomposition nyob rau hauv qhov kub thiab txias, muaj zog acid los yog muaj zog puag tej yam kev mob, tab sis nyob rau hauv tej yam kev mob, nws decomposition cov tshuaj tiv thaiv tej zaum yuav inhibited los yog txhawb.
Cov lus nug nquag
Dab tsi yog 5-Amino-1MQ ntxiv?
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5-Amino-1MQ ua zoo li "metabolic hloov flipper." Nws inhibits NNMT (nicotinamide N-methyltransferase), ib qho enzyme uas tuaj yeem cuam tshuam kev ua haujlwm metabolic thaum overexpressed. Los ntawm kev txo NNMT kev ua ub no, 5-Amino-1MQ boosts qib NAD+-ib coenzyme tseem ceeb koom nrog hauv kev tsim hluav taws xob.
Cov txiaj ntsig ntawm 5-Amino-1MQ yog dab tsi?
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Thaum xub thawj tsom rau cov metabolism, kev tshawb fawb pom NNMT nce nrog hnub nyoog / qhov hnyav ua rau muaj rog, tsis muaj zog, thiab NAD + poob. [30][31] High NNMT cuam tshuam nrog insulin tsis kam thiab rog rog hauv tib neeg. 5-Amino-1MQ txo NNMT, txhim kho cov rog, mob, tso zis mitochondrial, thiab kho cov leeg.
Dab tsi yog qhov txawv ntawm NAD + thiab 5-Amino-1MQ?
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NAD + kev kho mob pab kho cov qib depleted, thaum 5-Amino-1MQ pab txo qis npaum li cas cov qib tau siv sai. Los ntawm kev khaws cia ntau NAD + hauv lub xovtooj ntawm tes, ob txoj hauv kev no tuaj yeem ua kom muaj zog, ntev dua - txhawb nqa lub zog, kev ua haujlwm mitochondrial, kev tswj kev mob, thiab kho cellular.
Puas yog 5-Amino-1MQ txwv los ntawm Wada?
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Rau cov neeg ncaws pob lossis siab - cov neeg ua yeeb yam uas sib tw hauv kev ua kis las, qhov no tsis yog - cov ntsiab lus sib tham:5-Amino-1MQ raug txwv los ntawm World Anti-Doping Agency (WADA).
5-amino-1MQ cuam tshuam li cas rau cov metabolism?
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Nws ua haujlwm los ntawm inhibiting ib qho enzyme hu ua NNMT (nicotinamide N-methyltransferase), uas ua lub luag haujlwm hauvqeeb metabolismthiab nce rog cia thaum peb muaj hnub nyoog. Los ntawm kev thaiv NNMT, 5-Amino-1MQ tso cai rau koj lub hlwb siv lub zog ntau dua, hlawv rog sai dua, thiab khaws cov nqaij ntshiv.
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