P21 peptide ndiyosankha kwambiri zopangidwa peptide kuphatikiza ndi high brain chotchinga permeability. Zochokera ku kafukufuku wambiri pa ciliary neurotrophic factor (Mtengo CNTF), CNTF palokha ndizochitika mwachilengedwe cytokine mu neurons; a multifunctional neurotrophic factor.
Asayansi anapeza, komabe, kuti chilengedwe cha CNTF ndizovuta; zovuta kuwoloka magazi-ubongo chotchinga, immunogenicity zoopsa, ndi theka la moyo lalifupi kwambiri zonse zimapereka zovuta zazikulu pakufufuza zachipatala.
Kusanthula kwa kudumphadumpha ndi kuyesanso kobwerezabwereza kunapangitsa kuti pakhale chigawo chapakati., Ac-DGGL-NH₂. Kafukufuku wa in vitro adawonetsa kuti kachidutswachi kamakhalabe ndi zochita zambiri za neurotrophic, koma mphamvu zina zonse zochiritsira zinali zochepa.
Zopinga zazikuluzikulu ndizolepheretsa kulowa kwa magazi muubongo komanso kuyandikira kuwonongeka kwathunthu ndi ma plasma protease.; otsika kwambiri kupezeka kwa bioavailability mu vivo ndiye chotsatira.
Kuti athetse mavutowa kwambiri lipophilic tricyclic kapangidwe – adamantane gawo – adayambitsidwa. Kusintha uku kunapititsa patsogolo kuthekera kwa P21, cholepheretsa steric kupereka chitetezo pang'ono cha peptide's N-terminal kuchokera mapuloteni kuwukira.
Zakonzedwa bwino kukhazikika kwa metabolic ndipo moyo wotalikirapo kwambiri unatsatiridwa monga chotsatira chachindunji.
Zonse, gulu lapadera komanso lodziwika bwino la minyewa ndi machitidwe akukwaniritsidwa kudzera mu kapangidwe ka P21.
Kutsatizana
Ac-asp-gly-gly-leu-adamantane-NH2
Nambala ya CAS
/
Molecular Formula
C27H41N5O9
Kulemera kwa Maselo
579.65
Kafukufuku Wokhudzana ndi P21 Peptide
1.Biological Ntchito za CNTF
Kupitilira kulimbikitsa kupulumuka kwa motor neuron, kulimbikitsa mitundu yosiyanasiyana ya kaphatikizidwe ka neurotransmitter, kulimbikitsa kukula kwa neuronal axon, ndikuteteza ma neurons onse ndi ma cell awo othandizira excitotoxicity ndi mitundu ina ya kuwonongeka kotupa, CNTF imayendetsa njira zowonetsera mu hypothalamus – kuwonjezeka kukhuta kukhala chimodzi mwazolembedwa zolembedwa bwino.
2.Kuchita Kwachipatala ndi Neuroprotective Properties
Mayesero azachipatala awonetsa kuti P21 ili ndi ntchito yapamwamba kwambiri yamankhwala poyerekeza ndi CNTF. Hippocampal neurogenesis, mitundu yonse ya synaptic plasticity, luso la kuphunzira ndi zovuta zosiyanasiyana zachidziwitso zonse zimakhudzidwa.
Zotsatira za Neuroprotective (ischemia/reperfusion, neuroinflammation ndi kupsinjika kwa okosijeni) amawonedwanso, ndi kulamulidwa, pa p21.
3.Kulimbikitsa Neurogenesis ndi Kupititsa patsogolo Synaptic Plasticity
P21 imapanga chilengedwe chabwinoko kuti chichuluke, kusiyana, ndi kupulumuka kwa ma neuron atsopano.
Kusinthasintha kwa njira zowonetsera – MMENE/STAT kukhala woyamba, ndi umboni wina wa MAPK/ERK – ndi amene amachititsa izi.
Kuchulukitsa pulasitiki ya synaptic kudzera mukusintha kosawoneka bwino kwa 'mphamvu’ Kulumikizana kwa neuronal ndi njira ina yofunika kwambiri; luso la kuphunzira limagwirizana mwachindunji ndi njirayi.
Zitsanzo za zinyama zikuwonetsa zowonjezera kwambiri mu Kuthekera kwa nthawi yayitali (LTP) m'maselo a hippocampal, Kuphunzira kodalira ku hippocampus ndi kukumbukira kwamitundu yosiyanasiyana kumakulitsidwa chifukwa chake.
Kusungirako koyambira kwachidziwitso komanso kupangidwa kwaubongo kozungulira kumalimbikitsidwa ndi P21.
4.Ntchito ya Neuroprotective
Kuwongolera kwa intracellular antioxidant chitetezo network ndizodziwika bwino.
Kukhazikika kwa mitochondrial ntchito, kulepheretsa njira zina za apoptotic, ndi kuchepetsa (mopambanitsa) neuroinflammation zonse zimathandiza kuti chitetezo chitetezeke.
Imfa yoyeserera ya neuronal – mtundu wa ischemia-hypoxia, kapena posachedwapa matenda a Alzheimer akutsanzira poizoni – ikhoza kuletsedwa bwino ndi P21.
Kusunga umphumphu wa maselo a neuronal ndiye mapeto a mzere wa chitetezo; Njira zatsopano zochizira matenda enieni a neurodegenerative akufufuzidwa kudzera mu izi.
5.Kuwongolera Mphamvu Metabolism ndi Kulakalaka
Maphunziro oyambilira azachipatala a CNTF adawulula zotsatira zochepetsera thupi.
P21 imasungabe gawo lalikulu lomwe limayambitsa izi. Mayesero azachipatala amatsimikizira kulimbikira kwa zotsatirapo.
Njira ya leptin-STAT3 (hypothalamic) ndi momwe kafukufuku akuyendera; zizindikiro za satiety zimachulukitsidwa.
Kuchepetsa thupi kuchokera ku P21 ndikothandiza komanso, chofunika, kusunga minofu.
Kuzindikira kwa insulin kumawonjezekanso, Kukankhira P21 kupititsa patsogolo chithandizo choyenera cha kunenepa kwambiri ndi neurodegeneration yokhudzana.
COA
Mtengo wa HPLC
MS
