Adalank ke analogue ea maiketsetso ea peptide ea selank, ka phetoho e lebisitsoeng ea lik'hemik'hale.
Peptide e entsoe e le a e nkiloeng tsa nootropic lithethefatsi Selank, ka kenyelletso ea ts'ebetso ea acetylated N-terminal e ntlafatsang sebopeho sa eona sa adamantane-like sterically-constraining..
Phetoho ena e sebetsa e le motsoako o matla oa synergistic oa anxiolytic – motsoako oa nootropic Selank.
E qobisa mafutsana a Selank mokoallo oa mali-boko (BBB) ho phunyeletsa, ka tsela eo e eketsa tsamaiso ea methapo e bohareng ts'ebetso ea Adank haholo.
Keketso ea sehlopha sa acetyl e felisa tefiso e ntle ea sehlopha sa amino sa mahala sa N-terminal mme e fokotsa tefiso ea letlooa la peptide..
Phetoho ena ea physicochemical e ntlafatsa ntlha ea motlakase le thepa ea bokaholimo ba Adank, ho fokotsa likamano tse sa khetheheng tsa motlakase.
Ka hoo, molek'hule ea lithethefatsi e tšela mokoallo oa mali le boko habonolo haholoanyane ebe e fihla tsamaisong ea methapo e bohareng.
Ho feta moo, acetylation sireletsa Adank ho tloha exopeptidase ho senyeha 'me e eketsa haholo halofo ea bophelo ba eona ba vivo.
Sena se fana ka monyetla oa maemo a nako e telele a kalafo ea mali le ho fokotsa ho noa khafetsa.
Kenyelletso ea adamantane e theha "conformation core" e tsitsitseng ka har'a peptide ea Adalank.
Sena se fana ka tšekamelo e tsitsitseng ea sebaka ho peptide e tenyetsehang qalong., ho khothaletsa stereochemical conformation e hlokahalang bakeng sa ts'ebetso ea baeloji leha e le maemong a eona a sa tlamisoang.
Sena se ntlafatsa haholo bokhoni ba Adank ba ho tšela mokoallo oa mali le boko.
Holim'a moo, Adalank e bonts'a litlamorao tse itseng tsa immunomodulatory.
Tatelano
ac-thr-lys-pro-arg-pro-gly-pro-Adamanane-nh2
Nomoro ea CAS
/
Foromo ea limolek'hule
C46H75N13O10
Boima ba Molek'hule
970.19
Patlisiso ea Adank:
1.Mokhoa oa Ts'ebetso
Katleho-bohlale, Sebopeho se thata sa Adalank se lumellana haholoanyane le allosteric modulation sebaka sa GABA_A moamoheli alpha subunit, ho fana ka matla anxiolytic liphello.
Ho feta moo, karolo ea adamantane e nolofalletsa ho sebelisana ha hydrophobic ho Moamoheli oa NMDA sebaka sa mocha ho isa khalsiamo e leka-lekaneng le ho sireletsa khahlanong le kotsi ea excitotoxic.
Thepa ena e na le monyetla oa ho tshireletso ya methapo mefuteng ea kotsi ea boko ba ischemic le lefu la khatello ea maikutlo ka mor'a ho sithabela maikutlo (PTSD).
2.Anxiolytic Effects
Joalo ka karolo e ntlafalitsoeng ea Selank, Adalank e boloka tšebelisano e phahameng ea kamano le sebaka sa benzodiazepine ho GABA_A receptor α-subunit..
Leha ho le joalo, N-terminal acetylation le adamantane scaffold li tlosa mokhoa o tlamang ho tloha ho "flexible ho lekana hantle” ho “maema-kepeng a tiileng”.
Sena se matlafatsa GABAergic inhibitory neurotransmission, ho khothaletsa phallo ea chloride le phokotso e potlakileng ea ts'ebetso ho li-circuits tsa hyperactive amygdala-prefrontal cortex neural.
Ho fapana le benzodiazepines, Adalank e bonts'a khetho e phahameng ea receptor subtype, e nolofalletsang litlamorao tse tsitsitseng tsa anxiolytic ntle le sedation, ho phomola ha mesifa, kapa bokhoba ba bokhoba bo amanang le lithethefatsi tsa setso.
Ea eona index ea phekolo ke 3 ho 5 makhetlo a mangata, ho tšehetsa tsamaiso ea nako e telele ea lefu la ho tšoenyeha ka kakaretso le mathata a ho tšoenyeha ka maemo.
3.Ntlafatso ea Kelello le Ntlafatso ea Mehopolo
Adalank e thibela ka katleho ts'ebetsong ea tsela ea ho ruruha ea NF-κB le ho eketseha BDNF mRNA polelo ka 50%-80% ho hippocampus.
Sena se lebisa ts'ebetsong ea tlase Akt/CREB litsela tsa lipontšo, ho nolofatsa tlhahiso le tlhokomelo ea LTP.
E ntlafatsa haholo ho boloka memori ho ho qoba ho etsa letho liteko, e ntlafatsa thuto ea sebaka ka Motsoako oa metsi oa Morris, le lihanyetsi scopolamine-tšenyo e bakoang ke cholinergic.
Lintlha tsa preclinical li bonts'a hore Adalank e fokotsa liphoso tsa mohopolo o sebetsang ka 40%-60% hape e fokotsa ho fokotseha ha mohopolo oa tlhaho ho liphoofolo tse tsofetseng, e fana ka maikutlo a ho sebetsa mathateng a ho ithuta, bokooa bo fokolang ba kelello, le ho fokotseha ha memori e amanang le lilemo.
4.Liphello tsa Neuroprotective
Sebopeho sa adamantane ho Adalank se etsisa ketso ea memantine, ho sebetsa joalo ka motho ya hlokang tlhodisano Moamoheli oa NMDA mohanyetsi ea bakang thibelo e itšetlehileng ka voltage ea liteishene tse bulehileng le taolo ea fisioloji ea phallo ea calcium.
E fokotsa phallo ea mafu Ca²⁺ ka 60–70% ntle le ho senya lets'oao la Ca²⁺, ho fihlella profil e khethiloeng ea neuroprotective ntle le ho senya ts'ebetso e tloaelehileng.
Kahoo, liphuputso tsa preclinical li totobatsa bokhoni ba bohlokoa ba ho fetolela ba Adalank bakeng sa ho kenella kapele nakong ea stroke se matla, kotsi ea mokokotlo, le mafu a neurodegenerative.
COA
HPLC
MOF
