Shaanxi BLOOM Tech Co., Ltd. yog ib tug ntawm cov uas paub txog manufacturers thiab lwm tus neeg ntawm ace 031 peptide nyob rau hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo ace 031 peptide rau muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
ACE 031 peptideyog ib qho kev tshawb fawb tshiab tshiab -raws li peptide molecule uas tau ua tiav qhov kev hloov kho thiab kev ua kom zoo ntawm ActRIIB receptor. Nws txoj kev tsim qauv tsim los tswj cov kev taw qhia tseem ceeb xws li myostatin (GDF-8). Los ntawm kev xaiv khi thiab thaiv cov cim no, nws tuaj yeem maj mam thiab txhawb nqa cov protein synthesis thiab kev loj hlob ntawm cov leeg pob txha, yog li txhim kho cov leeg nqaij thiab lub zog. Cov molecule no tau ua kom pom lub hom phiaj zoo tshaj plaws thiab qhov tshwj xeeb hauv kev tshawb fawb preclinical, thiab nws cov txheej txheem ntawm kev ua haujlwm muab cov kev tshawb fawb tshiab thiab txoj hauv kev los txhawb cov leeg nqaij, txhim kho lub cev muaj pes tsawg leeg, thiab cov txheej txheem metabolic. Tam sim no, cov kev tshawb fawb muaj feem xyuam yog tsom mus rau kev tshawb nrhiav nws cov peev txheej hauv kev noj qab haus huv tshwj xeeb, sawv cev rau kev nce qib tseem ceeb hauv biotechnology hauv thaj chaw ntawm cov metabolism thiab kev tswj hwm lub cev. Qhov no nteg lub hauv paus kev tshawb fawb zoo rau kev txhim kho cov kev daws teeb meem ntsig txog kev noj qab haus huv yav tom ntej.
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ACE 031 Peptide COA
ACE 031 peptide(Myostatin inhibitory peptide 7) yog linear polypeptide muaj li ntawm 24 amino acids. Nws lub luag haujlwm tseem ceeb yog txhawm rau tiv thaiv cov teebmeem inhibitory ntawm myostatin thiab lwm yam kev tswj hwm tsis zoo ntawm cov leeg nqaij los ntawm kev khi rau lawv. Qhov no ua rau cov nqaij ntshiv. Cov txheej txheem tsim khoom suav nrog cov cuab yeej siv tshuaj lom neeg, kev ua kom huv huv, thiab kev tswj xyuas nruj. Kev tshuaj xyuas hauv qab no yog ua los ntawm peb qhov loj: kev tsim khoom, txheej txheem ntws, thiab kev sib tw.
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Manufacturing Principple: Lub hauv paus ntsiab lus ntawm kev siv tshuaj lom neeg
Kev tsim khoom ntawm ACE-031 cia siab rau cov khoom siv-theem peptide synthesis thev naus laus zis (SPPS), uas tau tsim los ntawm Merrifield hauv xyoo 1963 thiab nws tau txais Nobel nqi zog hauv Chemistry hauv xyoo 1984. Lub ntsiab lus tseem ceeb ntawm cov thev naus laus zis no yog kho cov carboxyl terminus ntawm amino acids rau hauv covalent cov khoom sib txuas. Los ntawm ib tug series ntawm "deprotection - activation - condensation" cov kauj ruam, cov peptide saw yog maj mam ncua. Tshwj xeeb rau ACE-031:
Resin xaiv:Xaiv cov resins haum rau C-terminal fixation (xws li Wang resin lossis Rink amide resin), kom ntseeg tau tias pawg carboxyl ntawm thawj cov amino acid (Ala) tsim cov ntawv cog lus ruaj khov nrog cov resin.
Tiv thaiv pab pawg tswv yim:Siv Fmoc (9-fluorenylmethoxycarbonyl) los yog Boc (tert-butoxycarbonyl) los tiv thaiv cov amino pawg, thiab sab saw tiv thaiv pawg (xws li Trt tiv thaiv Arg sab saw) los tiv thaiv sab kev tshwm sim. Piv txwv li, Fmoc tiv thaiv pab pawg yuav tsum tau muab tshem tawm raws li qhov tsis muaj zog alkaline (xws li 20% piperidine / DMF), thaum pawg tiv thaiv Boc xav tau kev kho mob nrog cov kua qaub (xws li TFA).
Coupling reagent:Siv cov tshuaj ua kom muaj zog xws li HBTU, HATU, lossis DCC / HOBt los txhawb kev tsim cov peptide bonds ntawm cov amino acids. Piv txwv li, thaum synthesizing Arg-Gln daim ntawv cog lus, lub sij hawm cov tshuaj tiv thaiv (feem ntau yog 1-2 teev) thiab kub (chav kub txog 40 degree) yuav tsum tau tswj kom meej meej kom tsis txhob muaj kev sib tw.
Txheej txheem khiav: Zoo tswj los ntawm raw khoom mus rau cov khoom tiav
Cov txheej txheem tsim khoom ntawm ACE-031 tuaj yeem muab faib ua tsib theem tseem ceeb:
Cov resin yog o nyob rau hauv DMF rau 30 feeb, thiab ces reacts nrog cov thawj amino acid (Fmoc-Ala-OH) nyob rau hauv tus neeg sawv cev coupling (xws li HBTU/DIPEA) rau 2 teev los tsim thawj peptide-resin complex.
Cov kauj ruam ntawm "deprotection - ntxuav - ua kom - condensation - ntxuav" yog rov qab siv cov cuab yeej siv hluav taws xob sib txuas, maj mam ntxiv 23 amino acids ntxiv. Piv txwv li, thaum synthesizing Trp-Arg daim ntawv cog lus, sab saw tiv thaiv pab pawg ntawm Trp (xws li Boc) yuav tsum tau ua kom zoo kom tsis txhob cuam tshuam nrog cov condensation ntawm Arg.
Cov peptide-resin complex yog kho nrog TFA/TIS/H₂O (95:2.5:2.5) rau 2 teev, txiav cov peptide saw ntawm cov cob thiab tshem tawm tag nrho cov pab pawg neeg tiv thaiv. Tom qab txiav, peptide yuav tsum tau precipitated nrog txias ether, thiab cov khoom crude yog sau los ntawm centrifugation.
Cov tshuaj purified peptide yog khov -qhuav kom tau cov hmoov dawb-zoo li cov khoom. Nws raug kaw thiab khaws cia hauv qab -20 degree, nyob rau hauv ib qho chaw tsaus thiab qhuav kom tsis txhob degradation.
Cov tshuaj purified polypeptide yog khov -qhuav kom tau cov hmoov dawb-zoo li cov khoom. Tom qab ntawd nws raug kaw thiab khaws cia hauv qab -20 degree, nyob rau hauv qhov chaw tsaus thiab qhuav kom tsis txhob degradation.
Kev nyuaj siab: Cov ntsiab lus tseem ceeb hauv kev tsim khoom
Kev tswj xyuas sab nraud
Hauv cov khoom-theem synthesis, impurities xws li peptides uas ploj lawm thiab tso peptides yog nquag tshwm sim. Piv txwv li, thaum synthesizing Gln-Asn daim ntawv cog lus, cov tshuaj tiv thaiv pH (7.5-8.0) yuav tsum tau tswj kom tsis txhob muaj asparagine translocation. Los ntawm optimizing tus neeg sawv cev sib txuas (xws li siv COMU hloov HBTU), qhov feem ntawm cov khoom lag luam tuaj yeem txo qis.
Ntev peptide synthesis efficiency
ACE-031 yog ib qho 24-peptide, thiab qhov kev pheej hmoo ntawm cov khoom tsim los ntawm- cov khoom sib sau thaum cov txheej txheem synthesis yog siab heev. Txoj kev "fragment condensation method" (ie, synthesizing 5-10 peptide fragments ua ntej, thiab tom qab ntawd txuas lawv los ntawm cov kua-theem method) tuaj yeem ua rau tag nrho cov txiaj ntsig. Piv txwv li, ACE-031 muab faib ua Ala-Trp-Arg (fragment 1), Gln-Asn-Thr-Arg (fragment 2), thiab lwm yam., thiab txhua qhov fragment yog synthesized nyias ua ntej splicing.
Cov qauv tswj kev ua tau zoo: Cov khoom tiav yuav tsum ua raws li cov ntsuas hauv qab no:
Purity: Qhov feem pua ntawm qhov siab tshaj plaws hauv cheeb tsam kuaj pom los ntawm HPLC yog ntau dua lossis sib npaug li 98%, thiab ib qho impurity tsawg dua lossis sib npaug li 0.5%;
Cov ntsiab lus: qhov yuam kev ntawm kev txheeb xyuas cov amino acid muaj pes tsawg leeg tsawg dua lossis sib npaug li ± 15%;
Solubility: Nws yog yooj yim soluble nyob rau hauv dej los yog DMSO, nrog ib tug concentration ntawm ntau tshaj los yog sib npaug rau 10 mg / mL yam tsis muaj nag lossis daus;
Kev ruaj ntseg: Lub purity ntawm ACE-031 tsis txo qis dua 2% thaum khaws cia ntawm -20℃rau 3 xyoos.
Daim Ntawv Thov thiab Kev Ua Lag Luam: Kev tshawb fawb- tau tsav kev tsim khoom xav tau
ACE 031 peptidefeem ntau yog siv rau hauv cov nqaij atrophy cov kab mob (xws li Duchenne cov leeg nqaij dystrophy), cov leeg loj hlob thiab kho kev tshawb fawb. Nws qhov kev tsim khoom yuav tsum ua raws li kev tshawb fawb-qib cov qauv. Tam sim no, cov neeg xa khoom tseem ceeb thoob ntiaj teb (xws li Shanghai Hong Peptide Biotechnology, MedChemExpress) muab cov kev pabcuam kev cai los ntawm cov khoom nyoos mus rau 98% purity, thiab xyuas kom meej cov khoom zoo los ntawm HPLC, MS, amino acid tsom xam, thiab lwm yam. Piv txwv li, Hong Peptide Biotechnology's ACE-031 khoom tau dhau SGS daim ntawv pov thawj thiab ua tau raws li cov kev cai ntawm SLAS.
ACE 031 peptide(Myostatin inhibitory peptide 7) yog ib qho recombinant protein uas inhibits cov kev ua ntawm myostatin thiab lwm yam tsis zoo regulators los ntawm kev khi rau lawv, yog li txhawb cov leeg kev loj hlob. Nws daim ntawv thov tseem ceeb yog nyob rau hauv ib puag ncig kev tshawb fawb thwmsim, thiab nruj me ntsis ua raws li cov txheej txheem rau dissolution, npaj, tswj, thiab cia yuav tsum tau. Cov hauv qab no yuav txheeb xyuas plaub yam tseem ceeb no.
Txoj Kev Txiav Txim Siab: Xaiv cov kuab tshuaj thiab kev ua haujlwm tshwj xeeb
Kev sib cais ntawm ACE-031 yuav tsum xaiv cov kuab tshuaj tsim nyog raws li nws lub cev thiab tshuaj lom neeg. Cov polypeptide no yog cov hmoov dawb, nrog rau qhov hnyav molecular ntawm 2956.49. Lub ntsiab lus isoelectric tsis paub tab sis tuaj yeem raug xam los ntawm cov amino acid muaj pes tsawg leeg hais txog nws cov solubility. Cov kauj ruam hauv qab no feem ntau siv hauv kev sim:
Kev xaiv cov kuab tshuaj
Sim siv cov dej tsis huv lossis PBS (pH 7.4) ua ntej. Yog tias qhov solubility tsis txaus, kho raws li cov khoom ntawm polypeptide. Rau ACE-031, yog tias nws muaj cov amino acids yooj yim (xws li Arg, Lys), sim 10% -30% acetic acid; yog tias nws muaj cov kua qaub amino acids (xws li Asp, Glu), siv 13% ammonia dej. Piv txwv li, hauv ib qho kev tshawb fawb, ACE-031 tau yaj hauv DMSO, tom qab ntawd diluted nrog PBS mus rau lub hom phiaj kom ntseeg tau tias qhov kawg ntawm DMSO concentration yog qis dua 1% kom tsis txhob muaj cytotoxicity.
Cov ntsiab lus tseem ceeb ua haujlwm
Ua ntej kev sib cais, rov qab kho cov polypeptide rau hauv chav tsev kub kom tsis txhob nqus dej noo; nrawm nrawm tom qab qhib lub hau lub raj mis kom txo tau lub sij hawm raug; siv ultrasonic lossis cua sov (tsawg dua lossis sib npaug li 50 degree) los pab kev tawg, tab sis tsis txhob kub siab ua rau denaturation; tom qab dissolution, aliquot thiab cia kom tsis txhob rov qab khov thiab thawing.
Kev npaj ua kom siab: Kev sim xav tau thiab suav ntau npaum li cas
Kev npaj siab ntawm ACE-031 yuav tsum tau txiav txim siab raws li cov qauv kev sim (xws li cov hlwb, tsiaj txhu) thiab kev tswj hwm txoj kev (xws li txhaj tshuaj, gavage). Cov txheej txheem kev npaj ua ke yog raws li hauv qab no:
Tsiaj sim
Kev txhaj tshuaj intramuscular ntawm posterior cranial fossa cov leeg hauv cov nas ua piv txwv, ACE-031 tau npaj ntawm qhov hnyav ntawm 5 mg / kg lub cev hnyav. Yog tias qhov hnyav nruab nrab ntawm cov nas yog 20 g thiab qhov ntim ntau npaum li cas yog 100 μL, ces qhov ntau npaum li cas rau ib tus nas=5 mg / kg × 0.02 kg=0.1 mg, thiab cov tshuaj ua haujlwm concentration=0.1 mg / 0.1 mL=1 mg / mL. Hauv kev sim, feem ntau nws yog qhov tsim nyog los npaj ib qho ntxiv 1-2 zaug ntawm cov tsiaj txhu los them rau kev poob.
Kev sim ntawm tes
Hauv C2C12 tus qauv sib txawv ntawm myotube, qhov sib txawv ntawm ACE-031 yog 10-100 nM. Piv txwv li, npaj 10 nM kev daws teeb meem: Noj 1 mg ntawm ACE-031 (molecular hnyav 2956.49), yaj hauv 1 mL DMSO kom tau txais cov tshuaj 1 mM Tshuag, thiab tom qab ntawd dilute nws 100,000 zaug nrog cov kab lis kev cai nruab nrab rau 10 nM.
Txoj kev tswj hwm: xaiv txoj kev thiab cov ntsiab lus ua haujlwm
Txoj kev tswj hwm ntawm ACE-031 yuav tsum raug xaiv raws li kev sim lub hom phiaj thiab tus qauv tsiaj. Txoj kev uas muaj xws li:
Kev txhaj tshuaj subcutaneous
Siv rau ntev - kev tswj hwm lub sijhawm (piv txwv li, 3 zaug hauv ib lub lis piam rau 5 lub lis piam) kom tswj cov ntshav cov tshuaj muaj zog. Piv txwv li, hauv cov qauv ntawm cov leeg nqaij atrophy hauv cov nas, kev txhaj tshuaj subcutaneous ntawm ACE-031 (10 mg / kg) ua rau cov leeg nqaij loj.
Kev txhaj tshuaj hauv zos
Lub hom phiaj rau cov leeg nqaij tshwj xeeb (xws li cov leeg nqaij tom qab cranial fossa), ua tiav siv lub microliter syringe. Thaum lub sijhawm ua haujlwm, tus tsiaj yuav tsum tau txhaj tshuaj loog (piv txwv li, nrog 2.5% Avertin tov), lub hom phiaj cov leeg yuav tsum raug nthuav tawm, cov koob tau muab tso rau hauv vertically thiab tom qab ntawd maj mam txhaj tshuaj kom tsis txhob muaj kua dej.
Cell tswj
Hauv kev sim hauv vitro, ACE-031 yog ntxiv ncaj qha rau hauv kab lis kev cai nruab nrab, ua kom cov ntshav tsis muaj ntshav kom tsis txhob muaj protein ntau. Piv txwv li, nyob rau hauv ib qho kev sim proliferation ntawm cov leeg satellite hlwb, tom qab kev kho mob nrog ACE-031 (50 nM) rau 48 teev, lub cell proliferation rate yog kuaj los ntawm EdU staining.
Cia tej yam kev mob: ruaj khov kho thiab ceev faj
Cov xwm txheej cia ntawm ACE-031 cuam tshuam ncaj qha rau nws cov haujlwm. Cov hauv paus ntsiab lus hauv qab no yuav tsum ua raws li:
Short - lub sij hawm cia
Cov tshuaj yaj yeeb yog pom zoo kom muab aliquoted rau hauv sterile EP raj thiab khaws cia ntawm -20℃los yog -80 degree, tsis txhob rov qab khov-thaw mus (tsawg dua los yog sib npaug li 3 zaug). Piv txwv li, nyob rau hauv ib qho kev tshawb fawb, ACE-031 cov tshuaj khaws cia ntawm -80℃rau 6 lub hlis tseem tuav ib qho kev ua ntawm Ntau dua lossis sib npaug rau 90%.
Ntev - lub sij hawm cia
Lub khov- cov hmoov qhuav qhuav yuav tsum tau muab ntim rau ntawm -80 degree, nrog rau desiccant tso rau hauv lub desiccator kom tiv thaiv kom tsis txhob ya raws. Cov hmoov tsis siv tom qab qhib lub raj mis yuav tsum tau siv kom sai li sai tau kom tsis txhob raug rau qhov chaw ntub dej.
Kev thauj mus los
Kev thauj mus los nrog cov dej khov qhuav, ua kom qhov kub thiab txias tsawg dua lossis sib npaug ntawm -70 degree, zam kev co uas yuav ua rau muaj protein ntau. Tom qab tau txais, tam sim ntawd xyuas qhov tseeb ntawm lub ntim thiab rov ua kom yaj raws li cov lus qhia.
FAQ
ACE-031 ua li cas?
ACE-031 yog ib daim ntawv soluble ntawm activin receptor hom IIB (ActRIIB). ACE-031 txhawb nqa cov leeg kev loj hlob los ntawm kev khi rau myostatin thiab lwm yam kev tswj tsis zoo ntawm cov leeg nqaij.
Puas yog ACE-031 yog myostatin inhibitor?
ACE-031 yog ib qho inhibitor ntawm myostatin thiab lwm yam cuam tshuam, ib txwm muaj cov proteins uas txwv cov leeg nqaij. Cov tshuaj sim ua raws li cov decoy receptor rau cov proteins no, ua kom lawv deb ntawm cov leeg nqaij. Nws yog tsim los tso cai rau cov nqaij ntshiv zoo dua thiab kho hauv DMD.
Dab tsi yog cov txiaj ntsig ntawm ACE peptides?
ACE ua lub luag haujlwm tseem ceeb hauv renin-angiotensin system, hloov angiotensin I mus rau angiotensin II, lub zog vasoconstrictor uas ua rau ntshav siab 8. Tsis tas li ntawd, ACE tseem muaj peev xwm ua kom tsis muaj zog bradykinin, vasodilatory peptide uas pab txo cov ntshav siab.
Dab tsi yog qhov txawv ntawm ACE 031 thiab Ace 083?
ACE-083 yog ib daim ntawv hloov kho ntawm ACE-031 thiab tsim los ua haujlwm hauv zos los tiv thaiv kev mob tshwm sim. Hauv Phase 1 kev sim, nws tau txhim kho cov leeg nqaij hauv zos tab sis tsis yog lub zog ntawm cov poj niam tom qab yug me nyuam.
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