ZiconotideAcetate yog peptide tshuaj muaj li D-phenylalanine - Ala, yog synthesized los ntawm rau Amino acids, thiab tom qab ntawd, txiav, huv, qhuav los ua khoom lag luam. Nws cov mis molecular yog c50h64n10o12s2, hnyav hnyav yog 1033.25, cas} {13}}. Nws yog dawb lossis yuav luag dawb xoob los yog hmoov. Ruaj khov nyob rau hauv acidic rau nruab nrab kev mob, tab sis tej zaum yuav tsis ruaj khov nyob rau hauv alkaline tej yam kev mob. Yooj yim rau yaj hauv dej thiab methanol, soluble me ntsis hauv ethanol, yuav luag Insoluble hauv ethero lossis chloroform. Feem ntau siv nyob rau hauv cov liaj teb ntawm biochemistry thiab tshuaj. Nws yog cov tshuaj tua kab mob uas muaj cov teebmeem hauv kev cuam tshuam rau ntau tus kab mob. Ib qho ntxiv, nws kuj tseem tuaj yeem siv rau hauv Vivo cov txheej txheem thiab kev tshawb nrhiav ua haujlwm, kev tshawb nrhiav kev ua suab, thiab lwm yam.
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Customized raj yas thiab corks:
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C.F |
C102H178N36O32S7 |
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E.M |
1463 |
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M.W |
1465 |
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m/z |
2644 (100.0%), 2643 (90.6%), 2645 (38.8%), 2646 (31.6%), 2645 (28.7%), 2646 (19.7%), 2645 (15.9%), 2645 (13.3%), 2647 (12.3%), 2644 (12.1%), 2646 (7.3%), 2646 (6.6%), 2645 (6.0%), 2648 (5.8%), 2645 (5.6%), 2647 (5.2%), 2644 (5.1%), 2647 (5.0%), 2648 (4.3%), 2647 (4.2%), 2647 (3.9%), 2646 (3.8%), 2647 (2.5%), 2648 (2.3%), 2646 (2.2%), 2648 (2.1%), 2645 (2.0%), 2647 (1.9%), 2644 (1.9%), 2649 (1.7%), 2649 (1.6%), 2647 (1.5%), 2647 (1.4%), 2646 (1.4%), 2645 (1.2%), 2648 (1.2%), 2647 (1.2%), 2648 (1.1%), 2644 (1.1%), 2647 (1.0%), 2647 (1.0%) |
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E.A |
C, 46.32; H, 6.78; N, 19.06; O, 19.35; S, 8.48 |
Cov tshuaj ntsuas hluavtaws synthesis ntawm acetic acid zeconomide feem ntau cuam tshuam nrog ntau cov kauj ruam, suav nrog amino acid condensation, kev hloov kho, cleavage, thiab purification. Vim tias cov tshuaj tiv thaiv nyuaj thiab cov kev sim ua kom pom tseeb muaj kev cuam tshuam nrog cov khoom siv hluav taws xob peptide, nws yog qhov yuav tsum muaj qee yam kev txawj ntse organic thiab kev txawj ntse. Cov hauv qab no yog cov tshuaj kuaj tshuaj synthesis txoj kev rauZiconotideAcetate:
1. Cov ntaub ntawv thiab reagents
Amino Acids: A Phenyylalanine - Ala, Gly, L-Ornithine, L-Tryptophan, thiab Cyster (lossis lawv cov thij derivatives).
Reagents: Acetic Athetharide, DCC, NMM, HPRC los ntawm Methanol thiab Acetoniturile, TLC Chromatogy silica gel, activated carbon.
Cov Khoom Siv: Teb Evaporator, muab cov chromatographyraphyraphy system, lub hnab lim dej, siab ua kua chromatography.
2. Cov kauj ruam ntawm tes hluav taws xob
(1) synthesis ntawm peptide saws: d-phenylalanine - ala, gly, l-tryptophan, thiab cys yog ntu sib txuas los ua peptide chains. Cov txheej txheem cua-theem peptide synthesis tau siv los tiv thaiv cov pawg amino Tom qab, lwm cov amino acid residues tau ua ntu zus ntxiv rau txhua pawg AMino
(2) Kev Txiav thiab Ua Tiav Peptide Synthesis, Peptide yog txiav tawm los ntawm cov khoom siv-theem Cov hau kev lim dej yuav suav nrog Gel reem chromatography (GFC), Rov qab ua kua chromatography (RP-HPLC), lossis capillary electrophoresis.
(3) Kev Hloov Kho thiab DEprotection: Hloov cov peptide peptide raws li xav tau, xws li ntxiv cov pab pawg ntxiv lossis ua lwm cov tshuaj lom neeg. Tom qab kev hloov kho, siv cov tshuaj reagrotection kom tshem tawm cov pab pawg uas muaj kev pab cuam uas pub dawb thiab tau txais daim ntawv dawb ntawm cov mob ziconotid acetate.
(4) Kev Ntsuam Xyuas thiab Kev Tswj Xyuas Zoo: Los ntawm ntau txoj kev ntsuas tshuaj yeeb (MSPR), thiab kev ua kom zoo nkauj
(5) Crystallization thiab cia: crystallize cov synthesized Zecanopeptide acetate kom txhim kho nws cov ruaj khov thiab huv. Tom qab crystallization, khaws lub muaju nyob rau hauv cov xwm txheej tsim nyog los tswj lawv txoj kev ruaj khov thiab huv.
Nyob rau hauv cov txheej txheem synthesis ntawmZiconotideAcetate, cov tshuaj tiv thaiv ntawm Ziconotid acetate nrog acetic anhydride kom tau txais cov acetate yog cov kauj ruam tseem ceeb. Ntawm no yog cov ncauj lus kom ntxaws thiab coj cov tshuaj sib txig sib luag.
Cov tshuaj tiv thaiv kab sib npaug ntawm cov ziconotid thiab acetic anhydride:
(Cnh2N+2O2Naj2+ (n +1) ch3Cooh → cnh2N+2O2Nch3Cooh + (n +1}) h2O)
Ntawm lawv, (CNH2n +2}}}}}} saib cov ziconotid.
Cov tshuaj tiv thaiv kab mob rau kev tshem tawm cov kev actetic anhydride:
(Cnh2n+2O2Nch3Cooh + h2O → cnh2N+2O2Naj2+ Ch3COOH)
Qhov kev tawm tsam no yog ib qho tshuaj tiv thaiv hydrolysis, uas txhawb nqa hydrolysis los ntawm kev kho tus nqi PH los ntawm hydrocloc acid lossis sodium hydroxide tov.
1. Cov cuab yeej sim thiab reagents
Cov Khoom Siv: Hlau nplaum Stirrer, Condenser Tube, txia funnel, puag ncig lub zog hluav taws xob, qeeb evaporator.
Reagents: Acetic anhydride, anhydrous pyridine, tolreene, hydrochloric acid, sodium hydroxide.
2. Kev sim ua kauj ruam
(1) Ntxiv Ziconotid thiab tus nqi tsim nyog ntawm anhydrous pyridine rau ib puag ncig hauv qab flask uas muaj lub sib nqus stirrer, thiab do tusyees.
(2) Maj mam ntxiv acetic anhydride rau cov tshuaj tiv thaiv kev sib xyaw thaum tswj qhov kub thiab txias hauv qab no 30 degree.
(3) Txuas ntxiv do nrog kev sib nqus quab yuam thaum cov txheej txheem tshuaj tiv thaiv thiab kev pom zoo saib cov tshuaj tiv thaiv. Thaum cov tshuaj tiv thaiv ua cov sib xyaw ua viscous, qhov ntsuas kub yuav tau nce ntxiv los txhawb kev tawm tsam.
(4) Tom qab cov tshuaj tiv thaiv tiav, ncuav cov tshuaj tiv thaiv sib xyaw rau hauv dej khov dej sib tov los txiav tawm cov tshuaj tiv thaiv.
(5) Tshem tawm cov kuab tshuaj thiab cov actict anhydride los ntawm cov teb chaws evaporator kom tau cov khoom nyoos.
(6) Purify cov khoom lag luam los ntawm kem chromatography mus ntxiv Purify z ficonol acetate.
(7) Kev ua suab paj tau raug kuaj pom los ntawm kev ua kom zoo chromatography los sau cov khoom lag luam phiaj.
Cov qauv molecular tsom xam ntawm acetidide tuaj yeem nqa tawm los ntawm cov hauv qab no:
1. Cov Txheej Txheem Yooj Yim
ZiconotideAcetate yog peptide tshuaj muaj ntau cov amino acids txuas nrog los ntawm peptide bonds. Raws li cov qauv molecular thiab molecular hnyav, cov qauv yooj yim ntawm cov qauv ziconotide acetate tuaj yeem txheeb xyuas.
Amino accusence Kev Tshawb Xyuas: Raws li molecular tus mis thiab molecular hnyav, amino acid lead ntawm acetic acid Zeconsping tuaj yeem ua tau zoo. Vim tias muaj cov d-phenylalanine, Ziceonotid acetate - Ala, gly, l-tryptophan, yog li kev sib txuas xaj thiab hom amino acids tau raug suav.
Kev txheeb xyuas tus qauv kev saib xyuas: Ziceonotid acetate muaj cov qauv kev sib txawv, uas muaj feem cuam tshuam nrog nws cov khoom siv tshuaj pharapacological thiab kev ua si lom. X-duab tshav crystallography resonance (NMR), thiab lwm yam kev sib xyaw tuaj yeem siv los xyuas cov qauv ntawm tus neeg txaus ntshai. Los ntawm cov tswv yim no, cov cuab yeej no, txoj kev hloov pauv ntawm acetic acid zeconomide ntawm qib atom tuaj yeem tau txais, thiab nws cov roj ntsha tau tuaj yeem kawm tau.
2. Kev Tshawb Xyuas Kev Ntsuas
Kev Tshawb Xyuas Kev Tshawb Fawb yog kev tshawb fawb ntawm kev kawm txog cov qauv peb-seem ntawm cov lwg me me. Kev tshawb xyuas kev tsom xam los ua kom nkag siab txog kev ua haujlwm roj ntsha thiab cov kws tshuaj papitalism ntawm kev ua ntawm cov qauv kev soj ntsuam hauv cov qauv molecular tsom. Piv txwv li, kev tsom xam ntawm amino acid configuration (D-hom lossis L-hom) tuaj yeem cuam tshuam rau kev ua yeeb yam tshuaj.
Ziconotide, Tseem hu ua prialt lossis intrathrecal Ziconotide (Heev xaiv N-hom calcium cov censionist muab tau los ntawm Conus Magus toxin. Nws ua rau muaj peev xwm ua tau zoo hauv kev tswj hwm qhov mob ntev los ntawm kev coj ua tshwj xeeb ntawm cov channel no, txo qis synaptic kis. Cov hauv qab no yog cov ncauj lus kom ntxaws ntxaws ntawm nws txoj kev txhim kho tom ntej:
Kev Lag Luam Muaj Peev Xwm
Nrog kev txhim kho kev ua kom ntev dua ntawm kev tswj hwm qhov mob, cov neeg mob 'xav tau kev ua tau zoo thiab qis tshwm sim cov tshuaj muaj nce. Raws li cov tshuaj tshiab thiab ua kom muaj txiaj ntsig zoo nkauj, cov compound no tau loj heev ua lag luam muaj peev xwm. Cov hauv qab no yog cov ncauj lus kom ntxaws ntxaws ntawm nws lub peev xwm ua lag luam:
- Nce tus neeg mob xav tau: Nrog rau cov neeg laus thiab kev nce qib txuas ntxiv, qhov kev thov kom muaj kev ua haujlwm zoo kuj tseem loj hlob. Ua ib qho tshuaj analgesic nrog ib qho tshwj xeeb mechanism ntawm kev nqis tes ua, nws tuaj yeem ua tau raws li cov kev xav tau ntawm pab pawg ntawm cov neeg mob thiab yog li ntawd muaj kev lag luam brocpections.
- Siv dav hauv chaw kuaj mob: nws tsis tuaj yeem siv los txo qhov mob ntev xws li mobileathic thiab mob cancer, tab sis kuj yog rau lwm hom kev tswj hwm mob. Qhov kev siv ntau no ua rau nws muaj kev sib tw hauv kev sib tw.
- Txoj Cai Pab Txhawb: Tsoomfwv nyob thoob plaws ntiaj teb txuas ntxiv txhawb lawv txoj kev txhawb nqa rau kev tswj hwm qhov mob thiab tau qhia txog cov cai muaj feem cuam tshuam. Qhov no muab txoj cai txoj cai txoj cai muaj zog rau kev txhim kho thiab kev txhawb nqa ntawm cov tshuaj no.
- Kev tshawb fawb thiab kev nthuav dav kev nce qib: nrog kev tshawb nrhiav tob ntawm nws cov tshuab ntawm kev nqis tes ua, nws cov kev tshawb fawb thiab kev txhim kho tau tas mus li ntxiv lawm. Yav tom ntej, nws yuav tsum ua kom tawg hauv kev kho ntau hom mob, yog li txuas ntxiv nws qhov chaw ua lag luam.
Kev Tshawb Fawb Kev Kawm thiab Kev Tshawb Fawb Yav Tom Ntej
Nyob rau hauv xyoo tsis ntev los no, muaj tau txais kev tshawb fawb tas mus li ntawm cov tshuaj no, tso lub hauv paus ruaj khov rau nws txoj kev txhim kho yav tom ntej kev txhim kho. Cov hauv qab no yog cov ncauj lus kom ntxaws tshuaj xyuas nws txoj kev tshawb fawb kev tshawb fawb thiab kev tshawb fawb yav tom ntej:
- Hauv kev tshawb nrhiav ntawm lub tshuab ntawm kev nqis tes ua: Cov kws tshawb nrhiav tau ua cov qauv tshawb fawb hauv qab ntawm Ziconomide ntawm Ziconium raws, pom nws cov cim kev sib txawv ntawm cov tshuab. Qhov no tsis tsuas pab peb nkag siab zoo dua nws cov nyhuv analgesic, tab sis kuj muab cov yeeb yam zoo rau nws txoj kev txhim kho kev tshuaj.
- Kev tshawb nrhiav cov qauv tshiab: Ntxiv rau kev tswj hwm qhov mob, cov kws tshawb nrhiav tseem tau tshawb txog cov tshuaj no hauv kev taw qhia. Piv txwv li, cov kev tshawb fawb tau pom tias nws yuav muaj kev cuam tshuam tshwm sim xws li antisepileptic thiab antidepressipressancy. Kev tshawb nrhiav ntawm cov kev qhia tshiab tshiab yuav txuas ntxiv nws daim ntawv thov tau piav.
- Kev ua kom zoo ntawm kev siv tshuaj tiv thaiv cov tshuaj: Txhawm rau txhim kho cov nyhuv analgesic thiab tus neeg mob ua raws li cov compound no, cov kws tshawb nrhiav tau kawm txog kev ua kom zoo dua nws cov tshuaj. Piv txwv li, los ntawm kev tsim cov khoom siv cov tshuaj tshiab lossis txhim kho cov qauv tshuaj uas twb muaj lawm, nws tuaj yeem yog lub hom phiaj mob, yog li txhim kho nws cov nyhuv.
- Kev tshawb fawb kev kho mob: Txhawm rau txhim kho cov nyhuv analgesic thiab txo cov kev mob tshwm sim, cov kws tshawb nrhiav tau tshawb txog kev kho cov tshuaj ntawm cov tshuaj no nrog lwm cov tshuaj. Los ntawm cov tshuaj tsim nyog ua ke thiab muab cov nyhuv ua ke, nws cov nyhuv analgesic tuaj yeem txhim kho ntxiv thiab cov kev pheej hmoo ntawm cov kev mob tshwm sim tuaj yeem txo.
Cim npe nrov: Ziceonotide Cas 107452-89-1, cov chaw muag khoom, chaw tsim khoom, Hoobkas, lag luam, yuav khoom, loj, rau muag