Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm met-enkephalinamide cas 60117-17-1 hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo met-enkephalinamide cas 60117-17-1 muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Tau ntsib -enkephalinamide, ib qho tshuaj lom neeg peptide derivative, belongs rau tsev neeg loj ntawm opioid peptides, muaj npe nrov rau lawv lub luag haujlwm hauv kev hloov kho qhov mob, kev xav, thiab kev tswj cov neurotransmitter tso tawm hauv nruab nrab thiab peripheral paj hlwb. Qhov kev sib xyaw tshwj xeeb no, ib daim ntawv amidated ntawm Met-enkephalin, tau txais kev hloov kho me me tab sis tseem khaws cov khoom siv tshuaj muaj zog.
Los ntawm kev hloov lub davhlau ya nyob twg carboxylic acid pawg nrog ib qho amide hauv Met-enkephalin, nws nthuav tawm kev ruaj ntseg tiv thaiv enzymatic degradation, tso cai rau nws mus ntev dua hauv kev lom neeg. Qhov kev txhim kho kev ruaj ntseg no txhais tau tias muaj peev xwm ua kom muaj txiaj ntsig zoo dua qub, suav nrog kev mob analgesia (mob nyem), sedation, thiab kev hloov pauv ntawm lub siab thiab qab los noj mov.
Nws ua feem ntau los ntawm kev khi rau opioid receptors, tshwj xeeb tshaj yog mu (μ) thiab delta (δ) subtypes, pib intracellular signaling cascades uas ua rau muaj ntau yam kev xav ntawm lub cev. Nws lub peev xwm kho tau raug tshawb nrhiav hauv kev kho mob ntev, qhov twg nws tuaj yeem muab lwm txoj hauv kev rau cov tshuaj opioid analgesics uas muaj kev phiv tsawg dua, xws li kev tiv thaiv kev tiv thaiv thiab kev nyuaj siab ua pa.
Txawm li cas los xij, txawm tias nws cov khoom muaj txiaj ntsig, nws txoj kev kho mob tau raug txwv vim muaj kev sib tw hauv kev xa cov peptides zoo hla cov ntshav- lub hlwb thaiv thiab ua kom muaj bioavailability txaus. Kev tshawb fawb tsis tu ncua tsom mus rau kev ua kom zoo tshaj plaws hauv kev xa khoom thiab tshawb nrhiav nws lub peev xwm hauv kev kho mob ua ke kom siv nws cov peev xwm kho mob tag nrho.
Customized Bottle Caps & Corks
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Tshuaj Formula |
C27H36N6O6S |
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Exact Mass |
572.24 |
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Molecular Luj |
572.68 |
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m/z |
572.24 (100.0%), 573.25 (29.2%), 574.24 (4.5%), 574.25 (4.1%), 573.24 (2.2%), 575.24 (1.3%), 574.25 (1.2%) |
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Elemental Analysis |
C, 56.63; H, 6.34; N, 14.68; O, 16.76; S, 5.60 |
Biological Activity thiab Receptor Interaction & Research Applications
Opioid Receptor Agonist: Ua raws li δ (delta) thiab ζ (zeta) opioid receptor agonist. Qhov no txhais tau tias nws khi rau thiab qhib cov receptors, ua rau muaj ntau yam teebmeem lom.
Inhibitory cuam tshuam: Nws tau pom tias inhibit pelvic paj hlwb -evoked contractions ntawm cov hnyuv distal hauv miv, nrog rau IC50 tus nqi ntawm 2.2 nM, qhia tias muaj zog inhibitory kev ua si ntawm tsawg concentrations.
Neuroscience: Vim nws cov opioid receptor agonism, nws yog siv hauv kev tshawb fawb neuroscience los kawm txog cov txheej txheem ntawm kev kho mob, kev quav tshuaj, thiab lwm yam opioid{0}} cov txheej txheem kho mob.
Cell Culture: Ntawm cov concentrations xws li 0.1 nM, 10 nM, thiab 1 μM, nws txo qis tag nrho cov glial hlwb hauv kab lis kev cai, ua rau nws yog ib qho tseem ceeb rau kev kawm glial cell biology.
Pharmacological Studies: Nws ua hauj lwm raws li ib tug lead compound rau txoj kev loj hlob ntawm tshiab analgesics thiab tshuaj tsom rau opioid receptors.
Drug Development & Materials Science thiab Nanotechnology & Lwm qhov chaw tshawb fawb
Cov Neeg Siv Tshuaj: Tau ntsib -enkephalinamidethiab nws cov derivatives raug tshawb nrhiav los ua cov neeg siv tshuaj muaj peev xwm rau kev kho mob, kev quav tshuaj, thiab lwm yam kev mob uas xav tau opioid receptor modulation.
Kev Kawm Preclinical: Nws tau dhau mus kuaj preclinical los ntsuas nws cov kev ua tau zoo, kev nyab xeeb, thiab cov tshuaj pharmacokinetics, paving txoj hauv kev rau kev sim tshuaj ntsuam xyuas.
Kev Hloov Kho Polypeptide: Siv nyob rau hauv kev sib txuas thiab kev hloov kho ntawm polypeptides, uas pom cov ntawv thov hauv cov ntaub ntawv tshawb fawb, xws li kev tsim cov khoom siv tshiab biomaterials.
Nanotechnology: Nws cov khoom siv tshuaj tshwj xeeb ua rau nws yog tus neeg sib tw tsim nyog rau kev siv nanotechnology daim ntawv thov, suav nrog kev tsim cov tshuab xa tshuaj thiab cov phiaj xwm kev kho mob.
Kev tshawb fawb kho mob: Tshaj li neuroscience thiab pharmacology, nws kuj tseem siv rau hauv kev tshawb fawb kho mob los kawm txog ntau yam txheej txheem lom neeg thiab cov kab mob uas opioid receptor modulation cuam tshuam.
Biotechnology: Nws ua lub luag haujlwm hauv kev tshawb fawb biotechnology, tshwj xeeb tshaj yog nyob rau hauv kev txhim kho cov cuab yeej tshiab thiab kev soj ntsuam.
Pharmacological teebmeem
Opioid Receptor Agonist Kev Ua Haujlwm
Delta (δ) Opioid Receptor Agonist: Ua tus agonist rau δ-opioid receptor, uas yog koom nrog ntau yam txheej txheem physiological. Qhov kev sib cuam tshuam no tuaj yeem ua rau muaj ntau yam teebmeem, suav nrog kev hloov kho ntawm qhov mob nkag siab, lub siab xav, thiab kev ntxhov siab.
Zeta (ζ) Opioid Receptor Agonist (Putative): Ntxiv nrog rau δ-opioid receptor, nws kuj tau tshaj tawm tias yog tus agonist rau putative ζ-opioid receptor, txawm hais tias lub luag haujlwm thiab kev ua haujlwm ntawm cov receptor no tseem nyob hauv kev tshawb nrhiav.
Cov teebmeem analgesic
Nws nthuav tawm cov tshuaj loog (mob-relieving) cov khoom los ntawm kev khi rau opioid receptors, tshwj xeeb tshaj yog cov δ-receptor. Qhov kev sib cuam tshuam no tuaj yeem txo qhov kev xav ntawm qhov mob thiab ua rau tag nrho cov nyhuv analgesic.
Nws tau raug pom tias inhibit pelvic paj hlwb -evoked contractions nyob rau hauv cov qauv tsiaj, qhia tias nws muaj peev xwm siv los tswj qhov mob visceral.
Modulation ntawm Neurotransmitter Tso Tawm
Los ntawm kev ua ntawm opioid receptors, nws tuaj yeem hloov kho qhov kev tso tawm ntawm cov neurotransmitters xws li norepinephrine, dopamine, thiab acetylcholine los ntawm neuronal terminals. Qhov no tuaj yeem ua rau muaj kev cuam tshuam rau ntau yam mob hlwb thiab puas siab puas ntsws.
Immunomodulatory teebmeem
Nws tau pom tias tswj kev tiv thaiv kab mob los ntawm kev cuam tshuam nrog opioid receptors ntawm lub cev tiv thaiv kab mob. Qhov no tuaj yeem ua rau kev hloov pauv ntawm cov lus teb inflammatory thiab yuav muaj peev xwm kho tau hauv autoimmune thiab inflammatory kab mob.
Cov teebmeem ntawm Cell Loj hlob thiab Kev Tsim Kho Tshiab
Raws li ib qho endogenous ligand rau opioid kev loj hlob zoo receptor (OGFR), nws tuaj yeem tswj cov ntaub so ntswg loj hlob thiab rov tsim dua tshiab. Qhov no qhia nws lub luag haujlwm muaj peev xwm hauv kev kho qhov txhab thiab kho cov ntaub so ntswg.
Cov teebmeem Neuroprotective
Los ntawm kev hloov kho neurotransmitter tso tawm thiab kev ua haujlwm receptor, nws kuj tseem tuaj yeem pom cov teebmeem neuroprotective, tiv thaiv neurons los ntawm kev puas tsuaj los ntawm ntau yam kev thuam xws li oxidative kev nyuaj siab thiab excitotoxicity.
Tau ntsib -enkephalinamideyog ib tug bioactive peptide nrog ib qho tseem ceeb physiological thiab pharmacological teebmeem. Thaum ua cov qauv molecular tsom xam, peb yuav delve rau hauv cov ntaub ntawv ntawm nws muaj pes tsawg leeg ntawm amino acids, theem nrab qauv, spatial conformation, thiab receptor binding.
Kev sib xyaw ntawm Amino Acids
Cov qauv molecular yog tsim los ntawm tsib amino acids, suav nrog methionine (Met), phenylalanine (Phe), glycine (Gly), aspartic acid (Tyr), thiab alanine (Ala). Cov amino acids no tau teem rau hauv ib qho kev txiav txim nyob rau hauv cov saw peptide, txiav txim siab lawv cov kev ua ub no thiab kev sib raug zoo ntawm cov qauv.
Secondary Structure
Cov qauv thib ob yog ib qho ntawm nws cov qauv tseem ceeb. Raws li kev sim cov ntaub ntawv thiab cov qauv theoretical, peb paub tias nws nyiam ua - Cov qauv kaum. Cov qauv no ruaj khov los ntawm kev sib cuam tshuam xws li hydrogen bonds thiab van der Waals rog, muab lub hauv paus rau nws cov txiaj ntsig zoo hauv cov kab mob nyob.
Spatial Conformation
Lub spatial conformation yog qhov tseem ceeb rau nws txoj kev khi rau receptors thiab kev ua haujlwm lom neeg. Cov kws tshawb fawb tau tshawb nrhiav nws qhov ua tau zoo ntawm qhov chaw los ntawm cov txheej txheem biophysical xws li nuclear magnetic resonance (NMR) thiab X-ray crystallography. Cov kev tshawb fawb no nthuav tawm nws lub xeev folding thiab muaj peev xwm ua tau peb - cov qauv ntawm qhov kev daws teeb meem, uas pab peb nkag siab txog nws cov txheej txheem ntawm kev cuam tshuam nrog receptors.
Txuas rau Receptors
Los ntawm kev khi rau opioid receptors, nws exerts nws physiological teebmeem xws li mob nyem thiab sedation. Lub receptor binding site cuam tshuam nrog ib feem ntawm nws cov qauv molecular los tsim cov qauv kev sib koom tes ruaj khov. Qhov kev sib xyaw ua ke no tsis tsuas yog cuam tshuam rau lub cev, tab sis kuj muaj kev cuam tshuam ntawm ntau theem xws li biochemistry thiab cellular transduction.
Hauv cov ntsiab lus,ntsib -enkephalinamide'sCov qauv molecular yog tus cwj pwm los ntawm nws qhov xwm txheej pentapeptide, nrog cov amino acid sib lawv liag xws li methionine, thiab muaj cov pab pawg ua haujlwm tshwj xeeb xws li peptide bonds, amino thiab amide pawg, thiab sulfur - muaj cov saw hlau sab. Cov yam ntxwv no ua rau nws cov tshuaj lom neeg thiab cov khoom siv lom neeg sib txawv.
Met Enkephalinamide yog ib qho kev hloov kho enkephalin analogue uas yog los ntawm endogenous opioid peptide tsev neeg. Nws yog structurally optimized raws li ntuj enkephalin, nrog ntau dua enzyme stability thiab muaj zog affinity rau opioid receptors.
Txij li thaum nws nrhiav tau nyob rau hauv 1970s, Met Enkephalinamide tau ua lub luag haujlwm tseem ceeb hauv neuropharmacology, kev tshawb fawb txog kev siv tshuaj kho mob, thiab kev tsim tshuaj.
Thaum ntxov xyoo 1970, cov kws tshawb fawb pom cov receptors hauv cov tsiaj txhu uas tshwj xeeb khi rau cov tshuaj opioid xws li morphine. Qhov kev tshawb pom no tau ua rau cov kws tshawb fawb xav tias tib neeg lub cev tuaj yeem tsim cov tshuaj zoo ib yam li opioids ntawm nws tus kheej.
Xyoo 1975, John Hughes thiab Hans Kosterlitz tau cais ob lub pentapeptides nrog opioid xws li kev ua los ntawm lub hlwb ntawm piglets - Met Enkephalin (Tyr Gly Gly Phe Met) thiab Leu Enkephalin (Tyr Gly Gly Phe Leu), sau ua ke hu ua enkephalins.
Qhov kev tshawb pom no nthuav tawm qhov muaj nyob ntawm endogenous opioid system thiab nteg lub hauv paus rau kev txhim kho cov tshuaj peptide tom ntej. Txawm hais tias enkephalins muaj cov nyhuv analgesic, lawv daim ntawv thov kev kho mob ntsib ob qho teeb meem loj:
Yooj yim rau degraded los ntawm enzymes: Enkephalin yog degraded sai los ntawm aminopeptidases (xws li N-terminal tyrosine hydrolases) thiab carboxypeptidases nyob rau hauv lub cev, nrog ib nrab - lub neej ntawm ob peb feeb xwb.
Cov ntshav tsis zoo- lub hlwb thaiv kev nkag mus rau hauv lub hlwb: Raws li cov polar peptide, enkephalin nyuaj dhau los ntawm cov ntshav-brain barrier (BBB), txwv nws lub hauv paus kev ua kom mob plab.
Txhawm rau txhim kho kev ruaj ntseg ntawm enkephalin, cov kws tshawb fawb tau siv cov tswv yim hauv qab no los hloov kho Met Enkephalin:
C-terminal amidation: Hloov C-terminal carboxyl pawg (- COOH) nrog ib qho amide (- CONH ₂) tuaj yeem tiv thaiv kev degradation los ntawm carboxypeptidases. Cov tshuaj hloov kho muaj npe hu ua Met Enkephalinamide (Tyr Gly Gly Phe Met NH ₂).
N-terminal tiv thaiv: Acetylation lossis cyclization ntawm N-terminal tyrosine kom ncua aminopeptidase hydrolysis.
D-amino acid hloov pauv: Hloov Gly ² lossis Phe ⁴ nrog D- hom amino acids kom txo qis enzymatic hydrolysis.
Piv rau ntuj Met Enkephalin, Met Enkephalinamide nthuav tawm:
Txhim kho enzyme stability: Lub hauv vitro ib nrab - lub neej tau txuas ntxiv los ntawm ob peb feeb mus rau ob peb feeb.
Enhanced receptor affinity: Qhov kev sib txuas affinity rau delta opioid receptor (DOR) thiab μ - opioid receptor (MOR) tau nce ntau.
Ntxiv cov nyhuv analgesic: Hauv kev sim tsiaj, lub sijhawm ntawm cov nyhuv analgesic ntawm kev txhaj tshuaj intrathecal nce los ntawm feeb mus rau teev.
Cov lus nug nquag
Vim li cas thiaj hu ua 'kev tshawb fawb tshuaj lom'? --Lub 'cliff effect' ntawm lethal koob txhaj tshuaj intravenously
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Nws yog ib qho muaj zog peptide opioid receptor agonist uas muaj zog heev, nrog rau cov koob tshuaj nruab nrab (LD ₅₀) qis li 20-30 mg / kg rau kev tswj hwm txoj hlab ntshav. Rau cov kab mob uas tsis tau kawm, lub qhov rais nruab nrab ntawm cov tshuaj tua kab mob thiab cov tshuaj analgesic zoo yog nqaim heev. Tsis zoo li ntuj Met enkephalin, uas tau rhuav tshem tag nrho hauv plasma hauv feeb, nws qhov kev hloov pauv hloov ua rau nws muaj qhov tsis txaus ntseeg enzyme stability. Qhov kev ruaj ntseg no tso cai rau cov tshuaj mus rau hauv lub cev tsis tu ncua, uas tuaj yeem ua rau muaj kev nyuaj siab ua pa nyuaj. Qhov no yog qhov laj thawj tseem ceeb vim li cas nws nyuaj rau pom hauv cov chaw tshawb fawb zoo tib yam - qhov kev pheej hmoo rov qab los txiav txim siab tias nws tsis tsim nyog siv los ua cov cuab yeej siv. Tom qab "kev tshawb fawb siv tsuas yog" ntawm nplooj ntawv cov ntaub ntawv yog qhov kev ceeb toom tseeb ntawm qhov "toxin qib" cov tshuaj pharmacological.
Puas yog nws 'amide tail' tiag tiag tsuas yog siv los tiv thaiv degradation? --Qhov hloov ntawm "agonist" mus rau "antagonist"
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C-terminal amidation tsis yog tsuas yog "cov ntaub thaiv npog" tiv thaiv kev puas tsuaj, tab sis kuj yog ib qho kev hloov pauv molecular uas tswj cov tshuaj siv tshuaj. Kev hloov kho me me ntawm tyrosine residues tuaj yeem hloov mus ua kom tiav kev ua haujlwm antagonist ntawm tib lub qaum. Ib txoj kev tshawb fawb loj hauv xyoo 1987 tau qhia tias thaum tyrosine residue ntawm Met enkephalin amide hloov los ntawm meta tyrosine (m-Tyr) los yog N-phenethyl meta tyrosine, lub molecule poob nws cov kev ua si excitatory thaum tswj siab affinity rau μ { morphine receptor binoid (i) opsimilate receptor binoid receptor binoid μ -. flipping mus rau hauv ib tug muaj zog thiab xaiv antagonist. Qhov no qhia tau hais tias cov pab pawg amide muab ib qho nruj 'docking platform' rau cov receptor, tso cai hloov maj mam hloov hauv cov saw hlau los txiav txim seb txoj kev taw qhia yog 'ntawm' lossis 'tawm'.
Puas yog nws ntaus nws tus kheej hauv kev daws teeb meem? --Qhov "tus kheej quenching" ntxiab ntawm nanoscale aggregation
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Hauv cov kev daws teeb meem siab heev (xws li cov npaj nrog DMSO), cov molecules yuav sib sau ua ke los ntawm π - π stacking ntawm cov amino acids uas muaj ntxhiab (tyrosine, phenylalanine), qhov tshwm sim hu ua "self quenching". Cov txiaj ntsig ntsuas tau qhia tias txawm hais tias nws cov solubility hauv PBS (pH 7.2) yog 2 mg / mL, nws cov solubility hauv DMSO siab dua (10 mg / mL). Txawm li cas los xij, qhov no 'siab concentration' yog ob -edged ntaj. Thaum hloov mus rau ib qho dej tsis sib haum, nws sai sai ua nanoscale aggregates vim hydrophobic kev sib tshuam. Qhov kev sib sau no tsis yog tsuas yog ua rau lub cev thaiv cov enzyme cleavage site (ua rau qis enzyme kinetics kev sim nyeem), tab sis kuj tseem tuaj yeem ua rau muaj qhov txawv txav ntawm keeb kwm yav dhau los fluorescence (vim lub zog hloov ntawm tyrosine residues), cuam tshuam rau qhov tseeb ntawm qhov kev sim.
Vim li cas nws tsis pom zoo kom yaj nws hauv "dej ntshiab" cia? --Tus ' menyuam ntsuag peptide' uas nws tus kheej devours
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Hauv cov dej ntshiab uas tsis muaj cov ntsev tsis muaj ntsev thiab cov khoom thauj khoom, nws ib nrab - lub neej tsuas yog ob peb teev, vim tias qhov tsis muaj cov tshuaj tiv thaiv tuaj yeem ua rau "tus kheej catalytic" degradation ntawm cov amino thiab carboxyl pawg hauv nws cov molecules. Raws li tus nqi me me peptide, nws txoj kev ruaj ntseg hauv cov kua dej yog nyob ntawm ion zog thiab pH tus nqi. Nyob rau hauv cov dej ntshiab (tshwj xeeb tshaj yog cov dej deionized), qhov tsis muaj kev tiv thaiv ion zoo ua rau khaus thiab tsis sib xws ntawm cov thermal txav ntawm cov molecules, ua rau muaj kev cuam tshuam ntawm intramolecular los yog intermolecular nucleophilic tawm tsam ntawm lub davhlau ya nyob twg thawj amine thiab carboxyl pawg (tsim diketopiperazine los yog zoo sib xws). Tus neeg muag khoom pom zoo cia cov xwm txheej yog 2-8 ° C qhuav thiab tsaus, uas tsis ncaj qha lees paub lawv "pickiness" ntawm qhov chaw daws teeb meem. Ib zaug nyob rau hauv ib qho chaw aqueous, nws yuav tsum tau siv ceev nrooj los yog khov khov.
Qhov kev pheej hmoo ntawm "racemization" zais nyob rau hauv cov txheej txheem ntawm synthesizing nws?
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Nyob rau hauv cov kauj ruam kawg ntawm "amidation" cov tshuaj tiv thaiv nyob rau hauv synthesis, kev siv cov pa carbodiimide (xws li EDCI) condensing agents tau yooj yim ua rau racemization ntawm C-terminal methionine residue. C-qhov kawg ntawm peptide yog methionine amide (Met NH ₂). Hauv cov khoom-theem lossis kua-theem synthesis, thaum dawb methionine txuas nrog cov amino pawg (NH3), cov pa condensing cov neeg ua haujlwm ua haujlwm carboxyl pawg los tsim cov khoom nruab nrab tsis ruaj khov. Vim yog acidity ntawm alpha hydrogen ntawm methionine residues (kho los ntawm amide bonds), proton capture thiab rearrangement yog heev yuav tshwm sim nyob rau hauv alkaline tej yam kev mob, ua rau tsim D-methionine isomers. Qhov no kuj yog vim li cas siab -purity Met enkephalin amides yog kim - cov txheej txheem feem ntau yuav tsum tau kim "racemic free condensates" los yog cov txheej txheem tshwj xeeb ua ntej ua kom tsis txhob muaj cov tshuaj tiv thaiv sab nraud.
Cim npe nrov: met-enkephalinamide cas 60117-17-1, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom