I-Adalank iyi-analogue ye-peptide yokwenziwa selank, ngokuguqulwa kwamakhemikhali okuhlosiwe.
I-peptide yakhelwe njenge-a okuphuma kokunye kwe i-nootropic izidakamizwa Selank, ngokungezwa kwe-acetylated N-terminal function ethuthukisa ukwakheka kwayo kwe-adamantane-like sterically-constraining.
Lokhu kuguqulwa kusebenza njenge-synergistic potentiator enamandla ye-anxiolytic – inhlanganisela ye-nootropic Selank.
Igwema abampofu bakaSelank umgoqo wegazi-ubuchopho (BBB) ukungena, ngalokho kwandisa isimiso sezinzwa esiphakathi umsebenzi we-Adalank kakhulu.
Ukwengezwa kwe- iqembu le-acetyl iqeda ukukhokhiswa okuhle kweqembu le-amino lamahhala le-N-terminal futhi yehlise inani eliphelele le-peptide.
Lokhu kulungiswa kwe-physicochemical kuthuthukisa i- iphuzu le-isoelectric kanye nezakhiwo ze-Adalank, ukunciphisa ukusebenzisana okungaqondile kwe-electrostatic.
Ngenxa yalokho, ingqamuzana lomuthi linqamula umgoqo wegazi nobuchopho kalula futhi lifinyelele ohlelweni lwezinzwa olumaphakathi.
Ngaphezu kwalokho, i-acetylation ivikela i-Adalank kusuka i-exopeptidase ukucekelwa phansi futhi nyusa ngokuphawulekayo isigamu sempilo yayo ye-vivo.
Lokhu kunikeza inzuzo yamazinga egazi okwelapha isikhathi eside futhi kunciphisa umthamo ovamile.
Ukufakwa kwe idamantane idala “umongo wokuguqula” ozinzile ku-peptide ye-Adalank.
Lokhu kunikeza umumo omisiwe wendawo ku-peptide yomugqa eguquguqukayo ekuqaleni., ukukhuthaza ukuhambisana kwe-stereochemical okudingekile emsebenzini webhayoloji ngisho sesimweni sakho esingaboshiwe.
Lokhu kulithuthukisa kakhulu ikhono lika-Adalank lokuwela umgoqo wegazi nobuchopho.
Ngaphezu kwalokho, I-Adalank ibonisa imiphumela ethile ye-immunomodulatory.
Ukulandelana
ac-thr-lys-pro-arg-pro-gly-pro-Adamanane-nh2
Inombolo ye-CAS
/
I-Molecular Formula
I-C46H75N13O10
Isisindo samangqamuzana
970.19
Ucwaningo lwe-Adalank:
1.Indlela Yokwenza
Ukusebenza kahle, Isakhiwo esiqinile se-Adalank sihambisana kakhulu ne ukuguqulwa kwe-allosteric indawo ye I-GABA_A umamukeli iyunithi ye-alpha, enikeza ngamandla i-anxiolytic imiphumela.
Ngaphezu kwalokho, i-adamantane moiety yenza ukusebenzisana kwe-hydrophobic ku- I-NMDA receptor indawo yesiteshi ukuya ekuthelelekeni okumaphakathi kwe-calcium nokuvikela ekulimaleni kwe-excitotoxic.
Lesi sakhiwo sinamandla okuthi neuroprotection kumamodeli okulimala kobuchopho be-ischemic kanye ukucindezeleka kwangemva kwenhlekelele (I-PTSD).
2.I-Anxiolytic Effects
Njengokususelwe okulungiselelwe kwe-Selank, I-Adalank igcina ukusebenzisana okuphezulu nesayithi ye-benzodiazepine ku-GABA_A receptor α-subunit.
Nokho, i-N-terminal acetylation kanye ne-adamantane scaffold susa imodi yokubopha kusuka “ku-flexible kufanelekile” kuya “kudokheni oluqondile oluqinile”.
Lokhu kuthuthukisa i-GABAergic inhibitory neurotransmission, ukukhuthaza ukungena kwe-chloride kanye nokunciphisa ngokushesha umsebenzi kuma-hyperactive amygdala-prefrontal cortex neural circuits.
Ngokuphambene ne-benzodiazepines, I-Adalank ikhombisa ukukhetha okuphezulu kwe-receptor subtype, inika amandla imiphumela eqhubekayo ye-anxiolytic ngaphandle kwe-sedation, ukuphumula kwemisipha, noma amandla okuba umlutha ahlobene nezidakamizwa zendabuko.
Yakho inkomba yokwelapha kuyinto 3 ku 5 izikhathi ezibanzi, ukusekela ukuphathwa kwesikhathi eside kwe ukukhathazeka okujwayelekile kanye nezinkinga zokukhathazeka zesimo.
3.Ukuthuthukisa Ingqondo Nokuthuthukiswa Kwenkumbulo
I-Adalank ivimbela ngokuphumelelayo ukusebenza kwendlela yokuvuvukala ye-NF-κB futhi iyanda I-BDNF mRNA inkulumo nge 50%-80% kwe i-hippocampus.
Lokhu kuholela ekusebenziseni umfula ongezansi Akt/I-CREB izindlela zokusayina, ukwenza lula ukungeniswa nokugcinwa kwe-LTP.
Ithuthukisa kakhulu ukugcinwa kwenkumbulo ngaphakathi ukugwema ukwenza okuthile izivivinyo, kuthuthukisa ukufunda kwendawo ku UMaze wamanzi kaMorris, kanye nokuphikisana i-scopolamine-ukulimala kwe-cholinergic.
Idatha ye-preclinical ibonisa ukuthi i-Adalank inciphisa amaphutha enkumbulo yokusebenza ngo 40%-60% futhi kunciphisa ukuncipha kwenkumbulo yemvelo ezilwaneni esezikhulile, ukuphakamisa ukusebenza ezinkingeni zokufunda, ukukhubazeka kwengqondo okuncane, kanye - nokuncipha kwenkumbulo ehlobene neminyaka.
4.I-Neuroprotective Effects
Isakhiwo se-adamantane ku-Adalank silingisa isenzo se i-memantine, esebenza njengomuntu ongaqhudelani I-NMDA receptor umphikisi obangela ukuvinjwa okuncike ku-voltage kweziteshi ezivulekile kanye nokulawulwa ngokomzimba kokungena kwe-calcium.
Yehlisa ukungena kwe-pathological Ca²⁺ ngo-60–70% ngaphandle kokuphazamisa ukusayina kwe-Ca²⁺ ye-physiological synaptic, ukufeza iphrofayili ye-neuroprotective ekhethiwe ngaphandle kokuphazamisa umsebenzi ojwayelekile.
Ngakho, izifundo zangaphambi komtholampilo ziqokomisa amandla abalulekile ka-Adalank okuhumusha okungenelela kusenesikhathi ku-stroke eyingozi, ukulimala komgogodla, futhi izifo ze-neurodegenerative.
I-COA
I-HPLC
MS
