Hauv kev tshawb nrhiav kev rog rog thiab kab mob metabolic,Adipotide Peptideyog ib tug revolutionary hluavtaws chimeric peptide tsim los ntawm MD Anderson Cancer Center nyob rau hauv 2004. Nws lub ntsiab tsim lub tswv yim yog txiav tawm cov ntshav mus rau adipose cov ntaub so ntswg thiab induce ischemic apoptosis nyob rau hauv adipocytes, txawv kiag li los ntawm tsoos qab los noj mov suppressants los yog metabolic regulators siv rau poob phaus. Cov peptide no yog tsim los ntawm lub hom phiaj cyclic peptide thiab ib qho apoptosis -nruj linear peptide txuas los ntawm thaj tsam luv luv. Nws muaj qhov hnyav molecular ntawm kwv yees li 2460 Da, thiab nws daim ntawv kev lag luam yog cov hmoov dawb lyophilized nrog cov dej solubility thiab kev ruaj ntseg siab.
🔬 Chimeric molecules induced los ntawm angiogenesis thiab apoptosis
Tshuaj,Adipotide peptideyog ib tug bifunctional chimeric peptide fused ua ke nrog ob functional modules: homing thiab tua. Nws cov txheej txheem ua ntu zus yog Cys-Lys-Gly-Gly-Arg-Ala-Lys-Asp-Cys-}NH₂-(KLAKLAK)₂, uas muaj nyob rau hauv ib qho kev sib txuas rau ib lub voj voog apoptosis{11}}inducing peptide ntawm Gly -Gly hloov tau yooj yim txuas. Lub cuaj N-terminal amino acid residues tsim ib tug disulfide-bonded cyclic qauv, tsim cov ntaub so ntswg adipose homing peptide. Qhov no cyclic qauv, stabilized los ntawm intramolecular disulfide bonds, imparts protease kuj thiab conformational rigidity, tsim lub hauv paus rau nws cov kev paub txog cov hlab ntsha adipose.
C-terminal apoptosis-inducing peptide (KLAKLAK)₂ yog cationic amphiphilic -helical peptide. Cov kab ke no suav nrog rov ua cov leucine thiab lysine residues, nqa ib qho txiaj ntsig zoo ntawm lub cev pH, ua kom muaj kev cuam tshuam electrostatic nrog rau qhov tsis zoo hauv cov mitochondrial membrane. Ib zaug hauv lub cell, cov peptide no ncaj qha cuam tshuam qhov kev ncaj ncees ntawm mitochondrial membrane, inducing tso tawm ntawm cytochrome c thiab pib apoptosis. Vim nws qhov tsis tshua muaj kev nkag mus ntawm cov plasma membrane ntawm cov hlwb ib txwm muaj, nws cov toxicity yog nyob ntawm homing peptides xa cov molecule mus rau lub hom phiaj ntawm tes, ua raws li internalization rau hauv lub cell. Qhov no prodrug-zoo li tsim spatial confines cov kev ua ntawm adipotide rau adipose cov ntaub so ntswg vascular endothelial hlwb, minimizing tawm - phiaj toxicity rau lwm cov ntaub so ntswg.
Lub cev, adipotide peptide, raws li kev tshawb nrhiav tshuaj, feem ntau yog muab los ua cov dawb kom tawm -cov hmoov dawb lyophilized nrog purity tsawg kawg yog 95% lossis 98%. Nws yog yooj yim soluble nyob rau hauv cov dej tsis muaj menyuam thiab yuav tsum tau muab cia rau ntawm -20℃los yog -80℃nyob rau hauv ib lub thawv kaw tiv thaiv los ntawm lub teeb. Rov qab khov-thaw cycles yuav tsum tau zam tom qab reconstitution. Nws qhov hnyav molecular yog kwv yees li 1900-2000 Da, faib nws raws li qhov nruab nrab- rau-luv saw peptide, thiab nws tuaj yeem ua tau loj-tsim siv cov txheej txheem txheej txheem peptide synthesis. Raws li cyclic peptide, qhov tseeb disulfide daim ntawv cog lus ua ke ntawm Adipotide ncaj qha cuam tshuam rau nws cov kev ua haujlwm lom neeg thiab kev ruaj ntseg; Yog li ntawd, kev tswj kom zoo yuav tsum suav nrog kev tshawb pom ntawm cov seem dawb thiol pawg siv Ellman's reagent.
Raws li txoj cai, Adipotide Peptide belongs rau tsev neeg "vascular targeting peptide". Nws lub homing peptide moiety tau pib kuaj los ntawm lub tsev qiv ntawv peptide random siv phage zaub technology. Nws tshwj xeeb khi rau cov txwv tsis pub muaj protein ntau, uas tau qhia ntau heev ntawm cov ntaub so ntswg adipose vascular endothelial hlwb. Prohibitin yog ib qho mitochondrial membrane protein ubiquitous nyob rau hauv ntau hom cell, tab sis nws yog txawv txav heev qhia rau daim nyias nyias ntawm adipose vascular endothelial hlwb nyob rau hauv cov neeg rog rog. Qhov kev tshawb pom no muab lub hom phiaj hauv paus rau "kev xaiv" ntawm Adipotide Peptide.
🧬 Kev rog rog thiab kev tshawb nrhiav kab mob metabolic, rog angiogenesis, kev tsim tshuaj
Cov kev siv tseem ceeb ntawmAdipotide peptideKev hloov pauv ntawm lub hom phiaj tshem tawm cov hlab ntsha adipose, induction ntawm adipocyte apoptosis, thiab kho cov kab mob metabolic. Spanning ntau cov lus qhia suav nrog kev tshawb fawb theoretical, tsiaj tus qauv kev tsim kho, kev txhim kho tshuaj tshiab, thiab kev tshawb nrhiav kev sib koom tes, nws yog ib qho kev sim uas tsis muaj peev xwm thiab cov khoom muaj nyob rau hauv kev tshawb fawb ntawm adipose biology thiab kab mob metabolic.
Hauv kev tshawb fawb txog kev rog rog thiab adipose ntshav hlab ntsha biology, peptide no yog tus qauv inducing tus neeg sawv cev rau elucidating txoj kev tswj adipose ntaub so ntswg angiogenesis, cell homeostasis, thiab apoptosis. Cov kws tshawb fawb siv nws los xaiv cov dawb adipose microvascular network hauv cov tsiaj sim, tsis tu ncua saib cov kev hloov pauv hauv adipocyte morphology, cov ntaub so ntswg inflammatory infiltration, thiab lipid metabolism, yog li qhia meej txog kev sib txuas ntawm cov ntaub so ntswg adipose thiab cov kab mob metabolic. Ib txhij, nws yog siv los sib piv qhov sib txawv ntawm vascular receptor qhia ntawm dawb thiab xim av adipose cov ntaub so ntswg, delving rau hauv lub hauv paus molecular ntawm lub hom phiaj pom nyob rau hauv cov ntaub so ntswg adipose, thiab accumulating yooj yim cov ntaub ntawv rau tom ntej lub hom phiaj formulation txoj kev loj hlob.
Nws tseem yog ib qho tseem ceeb rau kev tsim tsiaj cov qauv ntawm kev rog rog, hom 2 mob ntshav qab zib mellitus, metabolic syndrome, thiab tsis yog - haus dej cawv fatty siab kab mob, thiab rau kev soj ntsuam txog cov txheej txheem. Cov kws tshawb fawb tau muab cov tshuaj rau cov tsiaj sim classic xws li noj zaub mov - ntxias cov nas rog rog thiab rog rog rhesus liab. Cov tshuaj no txo qis subcutaneous thiab visceral rog cov ntsiab lus, ib txhij txo lub cev hnyav, ntshav qabzib, thiab ntshav lipid qib, thiab txhim kho insulin tsis kam. Raws li cov txheej txheem no, cov kws tshawb fawb tuaj yeem tshawb xyuas ncaj qha rau lub luag haujlwm ntawm cov ntaub so ntswg adipose ntau dhau los ntawm kev txhim kho cov kab mob metabolic thiab txheeb xyuas cov kab mob ntawm cov kab mob hauv cov kab mob physiological metabolism tom qab rog ablation.
Raws li lub ntsiab lus tseem ceeb rau adipose - tsom rau cov tshuaj vascular peptide, Adipotide Peptide tau coj txoj hauv kev tshiab rau rog -txo cov tshuaj txhim kho. Txawm hais tias qhov kev sim tshuaj thaum ntxov tau raug txiav tawm vim yog qhov tseem ceeb ntawm nephrotoxicity, nws cov txheej txheem ntawm kev ua haujlwm -inducing apoptosis los ntawm kev txiav cov ntshav txaus- rhuav tshem cov kev txwv ntawm cov roj ib txwm muaj - txo cov tshuaj tsim tawm. Ntau pab pawg tshawb fawb tau siv peptide's dual - tus qauv sau npe ua daim ntawv qhia txog kev hloov kho, ua kom lub hom phiaj thaj tsam, apoptosis ib ntus, thiab cov kab txuas txuas. Qhov no txhim kho cov ntaub so ntswg tsom qhov tseeb thaum txo cov kev mob tshwm sim ntawm cov kab mob hauv nruab nrog cev, txuas ntxiv txhim kho lub cim tshiab ntawm kev nyab xeeb thiab muaj txiaj ntsig zoo thiab txhim kho cov rog rog -txo cov kev kho mob.
Cov peptide no tseem ua lub luag haujlwm tseem ceeb hauv kev tshawb fawb ntawm kev sib tshuam ntawm kev rog thiab oncology. Cov kev tshawb fawb niaj hnub no tau lees paub tias cov ntaub so ntswg dawb adipose ntau dhau tsis tu ncua secretes inflammatory yam thiab loj hlob yam, indirectly txhawb qhov tshwm sim thiab kev loj hlob ntawm cov qog nqaij hlav xws li prostate cancer thiab cancer mis. Los ntawm kev siv adipotide peptides kom txo tau tag nrho lub cev rog thiab txo qhov tso tawm theem ntawm adipose- tau txais cov tshuaj bioactive, nws muaj peev xwm soj ntsuam qhov cuam tshuam ntawm cov ntaub so ntswg adipose ntawm cov qog loj hlob, tshawb nrhiav cov kab mob thiab cov txheej txheem muaj peev xwm cuam tshuam txog kev rog -cov qog nqaij hlav, thiab nthuav dav cov ntaub ntawv ciam teb ntawm peptide.
🎯 Lub hom phiaj khi → Internalization → Mitochondrial puas → Angiogenesis → rog necrosis
Adipotide peptideexerts nws cov kev ua tau zoo los ntawm ib tug ua tiav thiab hierarchical mechanism, los ntawm lub hom phiaj paub nyob rau hauv cov hlab ntsha mus rau intracellular biochemical cov tshuaj tiv thaiv, thiab thaum kawg mus rau kev hloov ntawm cov ntaub so ntswg thiab systemic theem. Nws yog lub hom phiaj ntawm adipose- cov hlab ntsha thoob plaws hauv cov txheej txheem, yam tsis muaj kev cuam tshuam nrog lub hauv paus paj hlwb kev ua haujlwm lossis cuam tshuam rau cov ntaub so ntswg ua haujlwm, ua kom pom qhov kev txiav txim siab tshwj xeeb.
Thaum cov peptide nkag mus rau hauv cov hlab ntsha, nws cov N-terminal cyclic targeting qauv, vam khom rau saum npoo thiab hydrophobic kev sib cuam tshuam, tshwj xeeb tshaj yog paub thiab khi rau receptor complexes ntawm cov dawb adipose vascular endothelial hlwb. Cov receptors tshwj xeeb no yog tsom rau ntawm phab ntsa sab hauv ntawm adipose microvessels; Cov hom phiaj zoo sib xws tsis tshua pom muaj nyob rau hauv endothelium ntawm cov hlab ntsha hauv lwm yam kabmob. Cov yam ntxwv no tso cai rau cov peptide molecule mus rau ntau qhov ntau nyob ib puag ncig cov ntaub so ntswg adipose, zam qhov tsis zoo ntawm kev nthuav dav - cov phiaj xwm los ntawm qhov chaw.
Tom qab khi, tus receptor-peptide complex nkag mus rau hauv cytoplasm ntawm endothelial hlwb ntawm clathrin-kho endocytosis, tso tag nrho peptide saw mus rau hauv lub cell sab hauv. Lub sijhawm no, ntu apoptotic peptide ntawm C-terminus, tsim los ntawm D-amino acids, pib ua haujlwm. Kev cia siab rau nws cov nqi zoo, nws nkag mus rau hauv mitochondrial membrane qauv thiab ntxig rau hauv phospholipid bilayer ntawm sab hauv mitochondrial membrane, ncaj qha cuam tshuam cov membrane kev ncaj ncees thiab ib txwm muaj peev xwm ntawm daim nyias nyias, ua rau mitochondrial o thiab cov txheej txheem rupture.
Tom qab kev puas tsuaj mitochondrial thiab rupture, ntau yam pro-apoptotic tshuaj, xws li cytochrome C thiab apoptosis-inducing yam, raug tso tawm rau hauv cytoplasm, activating cascade ntawm caspase tsev neeg cov proteins thiab pib tsim cov txheej txheem cell tuag nyob rau hauv vascular endothelial hlwb. Tom qab ua tiav apoptosis ntawm ntau cov adipose microvascular endothelial hlwb, tag nrho cov microvascular network maj mam poob, tag nrho cov hlab ntshav ntawm cov ntaub so ntswg adipose, ua rau muaj kev pheej hmoo ntawm ischemic thiab hypoxic ib puag ncig.
Kev tsis txaus ntawm cov pa oxygen thiab cov khoom noj khoom haus, adipocytes tsis tuaj yeem tswj hwm kev ua haujlwm ntawm lub cev, tom qab ntawd ua rau theem nrab apoptosis thiab cov ntaub so ntswg necrosis. Tag nrho cov ntim thiab qhov hnyav ntawm cov ntaub so ntswg adipose txo sai heev, nrog rau kev txo qis hauv visceral rog. Cov ntaub so ntswg necrotic adipose yog maj mam phagocytosed, decomposed, thiab tshem tawm los ntawm macrophages. Lub sij hawm luv luv - cov lus teb inflammatory uas tshwm sim thaum lub sij hawm cov txheej txheem no maj mam zuj zus raws li cov ntaub so ntswg clearance tiav, thiab cov mob inflammatory xeev ntawm cov ntaub so ntswg adipose yog txhim kho.
Tom qab tag nrho lub cev rog txo qis, qhov tso tawm ntawm cov kab mob inflammatory thiab cov rog dawb los ntawm cov ntaub so ntswg adipose yog txo qis. Lub cev rhiab heev ntawm cov tshuaj insulin maj mam rov zoo, cov ntshav qab zib thiab cov ntshav lipid qib rov qab mus rau qhov qub, daim siab steatosis tau txo qis, thiab ntau yam kab mob metabolic raug kho. Cov txheej txheem ntawm kev ua no tsuas yog txo cov naj npawb ntawm cov rog rog, tsis yog ua rau lawv qhov ntim ib ntus zuj zus. Yog li ntawd, cov rog - txo cov nyhuv yog ntev - kav ntev thiab tsis tshua muaj kev rov zoo. Tsis tas li ntawd, nws tsis cuam tshuam nrog lub chaw tswj kev qab los noj mov, yog li zam kev mob tshwm sim xws li anorexia thiab palpitations.
🔭Qhov kev sib tw ntawm nephrotoxicity thiab translational prospects ntawm kev kho mob ua ke
Txawm tias muaj kev cia siab muaj peev xwm ntawmAdipotide peptideHauv kev poob phaus thiab kev txhim kho metabolic, nws cov kev kho mob txhais tau raug cuam tshuam los ntawm nephrotoxicity. Nyob nruab nrab ntawm 2011 thiab 2015, adipotide peptide tau dhau los ntawm Phase I kev sim tshuaj. Cov kev tshawb fawb no tsom los ntsuas nws txoj kev nyab xeeb thiab kev zam rau cov neeg rog rog lossis rog rog nrog hom 2 mob ntshav qab zib thiab tshawb nrhiav nws qhov pib poob phaus. Cov txiaj ntsig tau lees paub tias adipotide tiag tiag ua rau qee qhov poob phaus thiab txhim kho insulin tsis kam. Txawm li cas los xij, cov ntaub ntawv kev nyab xeeb tau pom tias qee cov neeg tau ntsib cov koob tshuaj - txwv tsis pub nephrotoxicity, feem ntau tshwm sim raws li cov ntshav siab creatinine, proteinuria, thiab nce biomarkers ntawm lub raum tubular puas. Lub raum biopsy qhia tau hais tias muaj zog apoptosis ntawm lub raum tubular epithelial hlwb, uas yog txuam nrog kev qhia profile ntawm txwv tsis pub nyob rau hauv lub raum hlab ntsha. Yog li ntawd, kev txhim kho kho mob ntawm adipotide peptide raug tshem tawm lossis raug tshem tawm tom qab kev sim Phase I.
Cov patent portfolio thiab kev hloov kho cov tswv yim rau adipotide peptide feem ntau tsom rau txo nephrotoxicity. Kev txhim kho tom qab thib ob - tiam molecules feem ntau cuam tshuam nrog kev ua kom luv ib nrab - lub neej, hloov cov linkers los hloov cov txheej txheem metabolic, lossis qhia ntxiv "cov pab pawg tiv thaiv" rau hauv homing peptide. Lwm lub tswv yim yog los tsim "prodrug" cov ntaub ntawv uas tshwj xeeb qhib rau hauv cov ntaub so ntswg adipose microenvironment thiab nyob twj ywm hauv lub raum. Fusing adipotide peptide nrog cov tshuaj tiv thaiv -prohibitin cov tshuaj tiv thaiv uas siv cov tshuaj tiv thaiv kab mob- tshuaj conjugate thev naus laus zis tuaj yeem txhim kho lub hom phiaj ntxiv, tab sis qhov kev taw qhia no tseem nyob rau theem pib ntawm kev tshawb nrhiav.
Kev sib xyaw ua ke ntawm adipotide peptide nrog GLP-1 receptor agonists yog ib qho kev cog lus zoo heev. GLP-1 cov tshuaj xws li semaglutide ua kom poob phaus los ntawm centrally suppressing qab los noj mov, tab sis qhov hnyav rov qab yog tshwm sim tom qab txiav tawm.Adipotide peptide, ntawm qhov tod tes, ua haujlwm los ntawm lub cev cuam tshuam cov ntaub so ntswg adipose; kev sib xyaw ua ke ntawm ob yuav ua rau muaj kev sib koom ua ke ntawm kev poob phaus thiab kev saib xyuas qhov hnyav. Nephrotoxicity thiab immunogenicity yog cov teeb meem tseem ceeb uas ntsib kev txhim kho ntawm adipotide peptide. Txij li thaum adipotide yog ib qho khoom siv peptide tag nrho, nws yuav tsum tau theoretically tsis ua kom muaj zog tiv thaiv - tshuaj tiv thaiv zoo li cov tshuaj protein. Txawm li cas los xij, cov titers qis ntawm cov tshuaj tiv thaiv -Adipotide antibodies tseem raug kuaj pom hauv cov kev tshawb fawb ua ntej, thiab lawv qhov tseem ceeb ntawm kev kho mob tseem tsis tau meej.
Los ntawm qhov kev xav ntawm cov khoom xyaw tshuaj nquag (APIs), Adipotide peptide yog siab -purity, siab - nyuaj peptide raw khoom. Kev ua tau zoo ntawm nws cov kauj ruam cyclization thiab kev ruaj ntseg ntawm tus linker yog cov txheej txheem thev naus laus zis hauv kev txhim kho txheej txheem. Tus nqi kho mob ntawm Adipotide hauv kev rog rog thiab ntshav qab zib hom 2 yog tam sim no tseem nyob hauv "kev siv tau zoo, kev pheej hmoo tseem nyob" theem. Rau kev tshawb fawb thiab kev tsim kho tshuaj tam sim no, "vascular ablation" lub tswv yim nws sawv cev rau cov ntaub ntawv nthuav dav, txawm tias tsis zoo, kev sib tw nrog cov tshuaj GLP-1 booming.
Xaus
Adipotide peptide yog chimeric peptide uas tiv thaiv kev rog rog thiab insulin tsis kam los ntawm inducing apoptosis nyob rau hauv vascular endothelial hlwb ntawm dawb adipose ntaub so ntswg. Nws N-terminal cyclic homing peptide endows nws nrog lub peev xwm los tsom txwv, thaum nws C-terminal (KLAKLAK)₂ cationic peptide ua riam phom tua apoptosis. Txawm hais tias nws qhov kev sim tshuaj Phase I tau raug ncua ib ntus vim qhov rov qab nephrotoxicity, qhov hnyav poob ntawm 10%-15% thiab kev txhim kho metabolic tseem ceeb hauv cov qauv rhesus liab qhia tias nws cov hlab ntsha- lub hom phiaj tseem muaj peev xwm txhais lus loj heev. Kev siv tshuaj kom zoo, hloov kho nws cov qauv, lossis siv cov kev kho mob sib xyaw kom txo tau nws cov nephrotoxicity yuav yog qhov tseem ceeb rau seb qhov "adipose-vascular dab" tuaj yeem rov qab mus rau qhov chaw kho mob.
Xi'an Faithful BioTech Co., Ltd. cordially caw European cov tuam txhab tshuaj los koom tes nrog peb rau siab -zoo, sib tw nqiAdipotide peptide. Peb muab kev pabcuam rau cov neeg siv khoom, suav nrog cov ncauj lus kom ntxaws, cov khoom tshwj xeeb, thiab cov qauv kuaj, ua kom koj ntseeg siab rau qhov zoo thiab qhov tseeb ntawm peb cov khoom. Peb kuj muab cov ntaub ntawv ua tiav thiab kev tswj hwm kev tswj hwm, ua kom yooj yim rau koj cov txheej txheem kev yuav khoom thiab ua kom muaj kev lis kev cai zoo nyob hauv Europe.
Hu rau peb pab neeg muaj kev paub hnub no ntawmallen@faithfulbio.comlos tham txog koj cov kev xav tau tshwj xeeb thiab kawm txog vim li cas cov tuam txhab European ua lag luam xaiv Faithful ua lawv cov neeg muag khoom Adipotide peptide ntseeg.
Cov ntaub ntawv
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- Adipotide (PTD-DBM). (nd). AbMole BioScience (M54537).
- Prohibitin -Targeting peptide (Adipotide). (nd). Abcam (ab 284383).
- Adipotide (CKGGRAKDC-GG-(KLAKLAK)2). (nd). CPC Kev Tshawb Fawb (PEP-1335).
- Adipotide (PTD-DBM). (nd). MedChemExpress (HY-P1198).
- Kolonin, MG, et al. (2004). Reversal ntawm rog los ntawm lub hom phiaj ablation ntawm cov ntaub so ntswg adipose. Nature Medicine, 10(6), 625-632.
- Adipotide (PTD-DBM). (nd). TargetMol (T22106).