Colivelin(CAS 867021-83-8) yog ib qho hluavtaws hybrid peptide uas muaj 26 amino acids, nrog rau qhov hnyav molecular ntawm 2645.10 thiab cov mis molecular C₁₁₉H₂₀₆N₃₅O. Nws muaj plaub yam tseem ceeb: lub hlwb nkag mus, muaj zog neuroprotection, anti-apoptosis, thiab anti-A deposition. Ua kom los ntawm ob txoj hauv kev ntawm JAK / STAT3 thiab CaMKIV, nws tuaj yeem tiv thaiv cov neurons ntawm femtomolar concentrations, ua rau nws lub hnub qub peptide reagent rau kev tshawb fawb thiab kev tsim tshuaj hauv Alzheimer's kab mob, ischemic hlwb raug mob, thiab cov kab mob neurodegenerative.
Molecular tsim ntawm fused peptide chains
Tshuaj,Colivelinyog ib tug linear fusion peptide tsim los ntawm 26 amino acids, teej tug mus rau tsev neeg ntawm synthetically tsim hybrid neuropeptides. Nws ua tiav ib ntus los ntawm N-terminus rau C-terminus yog: serine-alanine-leucine-leucine-arginine-serine- isoleucine-proline-alanine-proline- alanine- glycine-alanine-serine-arginine-leucine-leucine-leucine-leucine-threonine-glycine-glutamic acid-isoleucine-aspartic acid-leucine-proline (H-Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala-Pro-Ala{{40}A2}Gly }}Ser-Arg-Leu-Leu-Leu-Leu-Thr-Gly-Glu-Ile-Asp-Leu}{5}OH{5}.
From a structural design perspective, Colivelin's construction follows a chimeric strategy of "complementary advantages." Its N-terminal nine amino acids comprise the active core fragment SALLRSIPA of an activity-dependent neurotrophic factor, which possesses independent neuroprotective activity and supports neuronal survival by activating the CaMKIV pathway. Its C-terminal 17 amino acids are derived from the highly active humanin derivative AGA-(C8R)-HNG17, which exerts its apoptosis-inhibiting effect by activating the STAT3 pathway. Flexible residues such as proline, alanine, and glycine act as "molecular hinges," ensuring that the two functional domains can fold independently in space and bind efficiently to their respective receptors or signaling molecules. This "hybrid" molecular design strategy allows Colivelin to inherit the functional advantages of both "parent" molecules, resulting in a synergistic effect greater than the sum of its parts (1+1>2).
Lub cev, siab -purity Colivelin yog ib qho dawb rau tawm -dawb lyophilized hmoov. Qhov no peptide yog hygroscopic heev; tus neeg muag khoom pom zoo kom khaws nws kaw, tiv thaiv lub teeb, thiab qhuav ntawm -20℃lossis -80℃. Reconstituted Tshuag daws yuav tsum tam sim aliquoted thiab khov; rov qab khov-thaw cycles yog nruj me ntsis txwv tsis pub tiv thaiv peptide saw degradation.
Hais txog solubility thiab stability,ColivelinNws yog yooj yim soluble nyob rau hauv sterile dej los yog phosphate tsis. Ib qho concentration ntawm 100 femtomolar Colivelin tuaj yeem cuam tshuam tag nrho amyloid- -induced neurotoxicity hauv vitro. Txawm li cas los xij, nws cov tshuaj aqueous nthuav tawm qhov tsis zoo nyob rau hauv chav tsev kub, feem ntau degrading hauv cov xuab moos. Qhov no yog ib qho tseem ceeb ntawm kev tsis sib haum xeeb los tiv thaiv nws txoj kev loj hlob ncaj qha mus rau hauv chav tsev -cov khoom siv tshuaj thauj khoom kub, txwv tsis pub nws siv los tshawb fawb cov tshuaj reagents.
Nyob rau hauv cov nqe lus ntawm kev noj tshuaj thiab kev xaiv, cov tshuaj recombinant raws li cov hmoov hmoov feem ntau siv tsis muaj saline rau kev sib cais thiab ntxiv ib qho me me ntawm bovine serum albumin raws li cov neeg nqa khoom noj protein kom txo tau qhov tsis yog - tshwj xeeb adsorption ntawm peptide mus rau lub raj phab ntsa. Tam sim no, siab -purity raw khoom muab los ntawm cov neeg muag khoom feem ntau muaj nyob rau hauv lyophilized hmoov los yog trifluoroacetate daim ntawv, nrog rau cov qauv purity yuav tsum nyob nruab nrab ntawm 95% thiab 98%.
Dual{0}} cav pib logic ntawm STAT3 thiab CaMKIV
Ntawm STAT3 signaling axis theem,Colivelinkhi rau ib qho tsis paub receptor ntawm lub cell membrane, nrhiav thiab ua kom Janus kinase 2 (JAK2). Ua kom muaj JAK2 phosphorylates STAT3 ntawm tyrosine residue 705. Phosphorylated STAT3 dimers thiab hloov mus rau hauv lub nucleus, khi rau DNA cov ntsiab lus teb ntawm cov hom phiaj txhawb nqa, txhawb nqa cov kev hloov pauv ntawm kev tiv thaiv -apoptotic proteins thiab pro- ciaj sia taus yam. Hauv tus qauv Alzheimer's tus kab mob, kev tswj hwm intranasal ntawm Colivelin nce qib STAT3 phosphorylation hauv septal - hippocampal cheeb tsam, ib qho kev hloov pauv ncaj qha thiab muaj txiaj ntsig zoo nrog kev txhim kho kev txawj ntse. Qhov tshwj xeeb, Colivelin qhov kev ua kom STAT3 tsis yog tsuas yog ua rau muaj kev loj hlob, tab sis qhov tseeb yog lub hom phiaj ntawm cov neurons los txhawb kev tiv thaiv -apoptotic signals.
Ntawm CaMKIV signaling axis theem, N-terminal fragment ADNF ntawm Colivelin ua rau ib qho kev ywj pheej receptor system, ua rau muaj kev txhawb nqa, me ntsis nce hauv intracellular calcium ion concentration. Thaum ua haujlwm, CaMKIV hloov pauv los ntawm cytoplasm mus rau hauv lub nucleus, phosphorylating qhov kev hloov pauv ntawm cAMP cov lus teb cov ntsiab lus -binding protein, thaum kawg txhawb kev nthuav qhia ntawm cov noob muaj txiaj ntsig zoo rau kev kho neuronal thiab kev ciaj sia, xws li lub hlwb- tau txais txiaj ntsig neurotrophic (BDNF). Ob txoj hauv kev no tau qhib ib txhij thiab ua haujlwm sib koom ua ke. Txawm hais tias ib txoj hauv kev raug thaiv, Colivelin tseem tuaj yeem tswj tau ib feem ntawm kev muaj sia nyob los ntawm kev cia siab rau lwm tus.
Hais txog kev tswj hwm kev hloov pauv ntawm cholinergic muaj nuj nqi, Colivelin kuj txhawb nqa cov noob qhia ntawm choline acetyltransferase thiab vesicular acetylcholine transporters los ntawm STAT3 signaling cascade. Nyob rau hauv tus qauv Alzheimer's kab mob, soluble A oligomers induce ib tug tseem ceeb txo nyob rau hauv tus naj npawb ntawm ChaT- zoo neurons nyob rau hauv lub medial septal nucleus; Intranasal kev tswj hwm ntawm Colivelin ua tau zoo thaiv qhov kev txo qis no thiab rov kho qhov kev ua haujlwm tsis zoo cholinergic. Qhov kev txhawb nqa dual no rau kev sib txuas neurotransmitter thiab kev thauj mus los yog lub hauv paus ua haujlwm rau nws txoj kev txhim kho ntawm kev nco tsis zoo.
Colivelin's calmotropic nyhuv yog qhov tseem ceeb thiab muaj kev nyab xeeb. Nws endogenous teeb liab activation yam ntxwv txiav txim siab tias nws tsis zoo li yuav ua rau excitotoxic puas tsuaj nyob rau hauv lub siab neurotoxic. Qhov kev sib xyaw ua ke ntawm cov muaj zog neuroprotection thiab tsis muaj tshuaj lom yog lub hauv paus tsim rau Colivelin qhov sawv tawm ntawm ntau cov neuropeptides thiab nws nkag mus rau hauv cov tshuaj txhais lus.
Anti-A Deposition thiab Anti- Cov teebmeem inflammatory
- Inhibition ntawm A aggregation: Ncaj nraim rau A ₁₋₄₂, tiv thaiv kev tsim cov tshuaj lom oligomers thiab fibrils, thiab txo cov amyloid plaques;
- Txhawb nqa ntawm A clearance: Upregulates LRP1 receptors, accelerating thauj A hla cov ntshav- hlwb teeb meem rau peripheral degradation;
- Microglia los tiv thaiv-inflammatory teebmeem: inhibits microglia ntau dhau, txo qhov kev tso tawm ntawm pro-inflammatory yam (TNF- , IL-1 ), thiab alleviates neuroinflammation.
Cov ntaub ntawv pov thawj los ntawm AD qauv thiab kev tiv thaiv ntawm septic intima
Colivelin feem ntau classic thiab zoo-cov ntaub ntawv siv yog raws li tus neeg sib tw kho mob Alzheimer's kab mob hauv kev tshawb fawb ua ntej. Nyob rau hauv ib daim ntawv qhia 2007, Chiba et al. thawj validated cov teebmeem neuroprotective ntawmColivelinhauv AD qauv siv cov kev coj cwj pwm thiab cov txheej txheem histochemical. Lawv pom tias Colivelin tuaj yeem thim rov qab scopolamine- lossis benzylcycloquinone-induced spatial memory impairment nyob rau hauv cov nas, txawm hais tias siv intraventricularly lossis intraperitoneally.
Hauv kev ntsuam xyuas kev coj tus cwj pwm tshwj xeeb, APP / PS1 ob npaug ntawm cov kab mob Alzheimer tus kab mob nas tus qauv yog "tus qauv kub" rau kev ntsuas cov tshuaj muaj peev xwm. Wu et al. pom tau hais tias ntev - lub sij hawm intranasal kev tswj hwm ntawm Colivelin tau txhim kho lub peev xwm paub txog cov khoom tshiab, kev ua haujlwm nco, thiab ntev - lub sij hawm spatial nco hauv 9- hli- qub APP/PS1 nas. Cov kev txhim kho kev coj tus cwj pwm tseem ceeb no tsis yog ib qho kev xav ntawm psychomotor excitation tab sis muaj feem cuam tshuam nrog kev cuam tshuam zoo ntawm kev muaj peev xwm mus sij hawm ntev hauv hippocampus, nrog rau kev txo qis hauv amyloid cov quav hniav.
Hauv kev sim tshawb nrhiav cov txheej txheem ntawm kev ua ntawm Colivelin, cov kws tshawb fawb tshwj xeeb tau taw qhia tias txawm tias nyob rau hauv cov ntsiab lus qis li 100 femtomolars, Colivelin zoo inhibited apoptosis induced los ntawm ntau yam AD-txog noob thiab -amyloid protein. Hauv qib subcellular, cov kws tshawb fawb tau siv cov tshuaj immunohistochemistry thiab Golgi staining kom pom tias Colivelin tuaj yeem txo qhov kev puas tsuaj ntawm soluble A oligomers ntawm postsynaptic density proteins.
Ib txoj kev tshawb fawb 2022 nthuav dav daim ntawv thov ntawmColivelinlos ntawm cov kab mob neurodegenerative mus rau sepsis hauv cov tshuaj kho mob tseem ceeb. Urban et al. tsim ib tus nas sepsis qauv siv cecal ligation thiab perforation, kuaj pom qhov tseem ceeb ntawm cov vascular endothelial glycocalyx core protein Syndecan-1 thiab mitochondrial puas. Kev txhaj tshuaj intraperitoneal ntawm 100-200 ug / kg ntawm Colivelin ib teev tom qab kev phais tau txhim kho sepsis ntsig txog vascular endothelial puas thiab glycocalyx shedding, thiab txo qis circulating theem ntawm inflammatory mediators xws li qog necrosis factor- . Kis electron microscopy ntawm kev kho mob ultrashort. mitochondria nyob rau hauv aortic endothelial hlwb.
Xyoo 2026, tus ntoo khaub lig- kab mob muaj peev xwm ntawm Colivelin tau nthuav dav ntxiv. Hauv kev tshawb fawb txog kev cuam tshuam ntawm Yin Chen Hao Tang ntawm tus qauv nas ntawm tus kab mob siab B, cov kws tshawb fawb tau teeb tsa ib pawg kev cuam tshuam nrog JAK2 cov neeg ua haujlwm los saib xyuas kev tiv thaiv ntawm kev thaiv Yin Chen Hao Tang. Cov txiaj ntsig tau pom tias Colivelin ib feem cuam tshuam rau lub siab ua haujlwm - txhim kho cov txiaj ntsig ntawm Yin Chen Hao Tang ntawm cov nas uas muaj kab mob siab thiab ua rau muaj kev nthuav tawm ntawm apoptosis proteins xws li caspase-3 thiab Bax, ntxiv kev lees paub tias Colivelin kuj ua haujlwm hauv lub siab los ntawm kev tswj hwm JAK2 / STAT3 txoj hauv kev.
Tus Tshiab Frontier hauv Intranasal Delivery thiab Anti-Mechanisms inflammatory
Hauv xyoo tas los no, kev tshawb fawb tsom mus ib puag ncigColivelintau hloov pauv los ntawm kev tshawb nrhiav nws cov teebmeem neuroprotective los daws qhov teeb meem tseem ceeb hauv kev kho mob txhais lus ntawm cov tshuaj peptide-kev xa khoom nruab nrab. Vim yog cov ntshav- lub hlwb thaiv kev tiv thaiv muaj zog tiv thaiv cov macromolecules feem ntau, xa Colivelin mus rau lub paj hlwb parenchyma yam tsis muaj kev puas tsuaj thiab nrog kev ua haujlwm siab yog qhov teeb meem tseem ceeb rau kev txhais lus kho mob. Ib txoj kev tshawb fawb tseem ceeb hauv xyoo 2007 tau pom tias tom qab siv cov tshuaj Colivelin rau hauv lub qhov ntswg ntawm cov nas, cov peptide molecules tuaj yeem hla cov ntshav- lub hlwb thaiv ncaj qha mus rau hauv nruab nrab lub paj hlwb los ntawm txoj kev olfactory paj hlwb, thiab cov kev ua ub no tseem ceeb tau kuaj pom hauv thaj tsam septal {{6} septal. Intranasal tswj, vim nws tsis yog -invasiveness, repeatability, thiab tus neeg mob txais, tau dhau los ua txoj kev xa khoom zoo tshaj plaws rau Colivelin.
Txhawm rau txhim kho cov metabolism hauv kev ruaj ntseg ntawm Colivelin, cov kws tshawb fawb tau tshawb nrhiav thiab ua kom zoo dua nws cov qauv. Cov kev tshawb fawb tau soj ntsuam qhov ua tau ntawm kev siv D-amino acid hloov pauv lossis hloov kho lub davhlau ya nyob twg hauv Colivelin thiab nws cov analogues. Cov tswv yim cyclization qauv kuj tau siv los txhim kho nws cov kev tiv thaiv rau protease hydrolysis.
Hauv txoj kev taw qhia Stat3, Colivelin tau hloov zuj zus los ntawm ib qho kev tshawb fawb nkaus xwb rau hauv kev cuam tshuam rau kev tswj hwm lub cev tiv thaiv kab mob polarization. Hauv kev cuam tshuam tom qab sepsis, Colivelin's systemic anti-inflammatory effect yog ib feem ntawm nws lub peev xwm los cuam tshuam macrophage polarization, hloov lawv los ntawm M1 pro-inflammatory phenotype mus rau M2 kho phenotype. Qhov kev hloov kho ntawm lub cev tiv thaiv kab mob hauv lub cev no muab kev nkag siab tshiab rau nws daim ntawv thov hauv ischemia-kev raug mob rov qab thiab autoimmune encephalomyelitis.
Raws li qhov siab -purity lom reagent, Colivelin yog tam sim no ua lag luam feem ntau tsim los ntawm cov khoom siv -theem peptide synthesis. Pawg C-terminal carboxyl pawg yog capped nrog ib pawg amide los txhim kho nws hauv vivo stability. Vim nws txoj kev ua ntu zus ntev thiab ntau yam leucine rov ua dua, tshem tawm peptides thiab qhov yuam kev nkag tau yooj yim tsim thaum lub sijhawm sib txuas, xav kom cov tuam txhab muaj kev hloov pauv siab heev -theem siab- ua haujlwm ua kua chromatography purification muaj peev xwm thiab kev tswj xyuas zoo.
Colivelin kuj qhia tau tias muaj peev xwm tiv thaiv tau hauv cov tshuaj kho tsiaj. Cov kev tshawb fawb ntawm fetal alcohol syndrome tau qhia tias nyob rau hauv ib qho ethanol- nthuav tawm cov qauv nqaij qaib embryo, Colivelin pretreatment tuaj yeem cawm apoptosis ntawm lub cev muaj zog neurons, ua kom pom nws qhov dav -spectrum tiv thaiv muaj peev xwm tiv thaiv lub hauv paus paj hlwb hauv kev loj hlob thaum ntxov.
Xaus
Colivelin, nrog nws qhov kev txawj ntse 26aa heterozygous peptide tsim, ua tiav plaub qhov txiaj ntsig zoo -femtomolar- qib muaj zog neuroprotection, hlwb nkag mus, tiv thaiv-A , thiab kev tiv thaiv synaptic-los ntawm synaptic dual- txoj kev sib koom ua ke. Qhov no ua rau nws yog qhov ntsuas peptide molecule rau kev tshawb nrhiav kab mob neurodegenerative thiab kev tsim tshuaj. Humanin-ADNF fusion caj qaum ntawm qib molecular structural lays lub hauv paus rau dual- txoj kev ua kom thiab ultra{10}} ua haujlwm siab.
Xi'an Faithful BioTech Co., Ltd. siv cov cuab yeej siv siab heev thiab cov txheej txheem los xyuas kom meej - cov khoom zoo. PebColivelinua tau raws li cov qauv tshuaj thoob ntiaj teb. Peb nrhiav kev ua tau zoo, tus nqi tsim nyog, thiab kev pabcuam zoo tshaj plaws ua rau peb nyiam tus khub rau cov tsev kho mob thiab cov kws tshawb fawb thoob ntiaj teb. Yog tias koj xav tau kev tshawb fawb lossis kev tsim khoom ntawm Colivelin, thov hu rau peb pab neeg ua haujlwm ntawmallen@faithfulbio.com.
Cov ntaub ntawv
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- Selleck Tshuaj. (2026). Colivelin (S9664) datasheet.
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