IP21 peptide ikhethwa kakhulu eyenziweyo peptide i-compound ene-high barrier barrier permeability. Ithathwe kuphando olubanzi kwi i-ciliary neurotrophic factor (CNTF), I-CNTF ngokwayo yenzeka ngokwendalo icytokine ngaphakathi kwemithambo-luvo; i-multifunctional i-neurotrophic factor.
Izazinzulu ziye zafumanisa, nangona kunjalo, ukuba ulwakhiwo lwendalo lwe-CNTF lunzima; ubunzima bokuwela i umqobo wegazi-ubuchopho, ukukhuseleka komzimba imingcipheko, kunye nesiqingatha sobomi obufutshane kakhulu zonke zinika imingeni ebalulekileyo yophando lwezonyango.
Uhlalutyo lwe-truncation kunye neemvavanyo eziphindaphindiweyo eziye zakhokelela ekuchongweni kweqhekeza elingundoqo., I-Ac-DGGL-NH₂. Uphononongo lwe-in vitro lubonise ukuba esi siqwenga sigcina umsebenzi olungileyo woqobo we-neurotrophic, kodwa onke amandla onyango angaphaya kwaye ahlala elinganiselwe.
Imiqobo ephambili kukunganyameki kakuhle komqobo wegazi-ubuchopho kwaye kufutshane nokonakaliswa okukhawulezileyo ziiplasma proteases.; isezantsi kakhulu bioavailability kwi-vivo sisiphumo sokugqibela.
Ukujongana nale miba i-lipophilic tricyclic structure – i-adamantane inxalenye – yaziswa. Olu hlengahlengiso luphucule ngempumelelo i-P21's permeability, isithintelo sesteric ukubonelela ngokhuseleko oluyinxenye lwe-N-terminal ye-peptide ukusuka iprotease uhlaselo.
Iphuculwe uzinzo lwe-metabolic kwaye isiqingatha sobomi obandisiweyo silandelwe njengesiphumo esithe ngqo.
Kuko konke, iseti eyodwa kunye echazwe kakuhle ye-neurological and behavioral effects iphunyezwa ngoyilo lweP21.
Ulandelelwano
Ac–asp-gly-gly-leu-adamantane-NH2
Inombolo yeCAS
/
Ifomula yeemolekyuli
I-C27H41N5O9
Ubunzima beMolekyuli
579.65
UPhando oluNxulumene nePeptide yeP21
1.Imisebenzi yebhayoloji ye-CNTF
Ngaphandle kokukhuthaza ukusinda kwe-motor neuron, ukuvuselela iindlela ezahlukeneyo ze-neurotransmitter synthesis, ikhuthaza ukukhula kwe-neuronal axon, kunye nokukhusela zombini ii-neuron kunye neeseli zazo ezixhasayo ukusuka excitotoxicity kunye neentlobo ezithile zomonakalo ovuthayo, I-CNTF ivula iindlela ezithile zokubonisa kwi-hypothalamus – ukwanda kokuhlutha kuba yenye yeziphumo ezibhalwe kakuhle.
2.Ukusebenza kweKlinikhi kunye neePropati zeNeuroprotective
Ulingo lwezonyango lubonise i-P21 ukuba inomsebenzi obalaseleyo we-pharmacological xa kuthelekiswa ne-CNTF. I-Hippocampal neurogenesis, zonke iintlobo ze iplastiki ye-synaptic, amandla okufunda kunye neentlobo ezahlukeneyo zokuphazamiseka kwengqondo zonke zinempembelelo entle.
Iziphumo ze-neuroprotective (ischemia/reperfusion, neuroinflammation kwaye uxinzelelo lwe-oxidative) nazo zibonwa, kwaye ilawulwa, nge p21.
3.Ukukhuthaza i-Neurogenesis kunye nokuphucula i-Synaptic Plasticity
I-P21 yenza i-microenvironment efanelekileyo yokwandisa, umahluko, kunye nokusinda kwee-neuron ezintsha.
Ukumodareyithwa kweendlela ezithile zomqondiso – NJANI/STAT ukuba ngowokuqala, ngobunye ubungqina be-MAPK/ERK – unoxanduva lwesi siphumo.
Ukwandisa iplastiki ye-synaptic ngokusebenzisa utshintsho olufihlakeleyo 'kumandla’ yonxibelelwano lwe-neuronal yenye indlela ephambili; amandla okufunda anxulumene ngqo nale nkqubo.
Iimodeli zezilwanyana zibonisa uphuculo olubalulekileyo kwi Ukwazi ixesha elide (LTP) ngaphakathi kweeseli zehippocampal, Ukufunda okuxhomekeke kwihippocampus kunye neendlela ezahlukeneyo zememori ziphuculwa ngenxa yoko.
Uvimba osisiseko wokuqonda kunye nayo yonke iplastiki yengqondo ejikelezileyo ngoko yongezwa yiP21.
4.Umsebenzi weNeuroprotective
Ukunyuswa kwe-intracellular antioxidant network networks yimpembelelo ebhalwe kakuhle.
Ukuzinzisa umsebenzi we-mitochondrial, uthintelo lweendlela ezithile zeapoptotic, kunye nokunciphisa (ngokugqithisileyo) i-neuroinflammation yonke inegalelo kwimeko yokukhusela.
Ukufa okulingelwe kwi-neuronal – uhlobo lwe-ischemia-hypoxia, okanye kutshanje isifo se-Alzheimer silinganisa i-toxins – inokuthintelwa ngokusebenzayo yi P21.
Ukugcina ubuncinci be-neuronal cell integrity yindawo yokugqibela yalo mgca wokukhusela; Iindlela ezintsha zonyango zezifo zokwenyani ze-neurodeergenerative ziyaphononongwa ngayo.
5.Ukulawulwa kwe-Energy Metabolism kunye ne-Appetite
Uphononongo lokuqala lweklinikhi lwe-CNTF luveze iziphumo ezinamandla zokuncipha kobunzima.
I-P21 igcina iqhekeza eliphambili elinoxanduva lwaloo nto. Izilingo zeklinikhi ziqinisekisa ukuqhubeka kwesiphumo.
Indlela yeleptin-STAT3 (i-hypothalamic) lugqaliselo lwangoku lophando; iimpawu zokuhlutha ziyandiswa.
Ukwehla kobunzima obuvela kwi-P21 kuyasebenza kwaye, okubalulekileyo, ukugcina izihlunu.
Uvakalelo lwe-insulin luyaphucuka, ukutyhalela phambili i-P21 kunyango olunokubakho lokutyeba kakhulu kunye ne-neurodegeneration enxulumeneyo.
I-COA
HPLC
NKSK
