Adalank ndeye synthetic peptide analogue ye selank, ine kunangwa kwemakemikari-alteration.
Iyo peptide yakagadzirwa sea derivative ye nootropic mushonga Selank, pamwe nekuwedzera kweacetylated N-terminal basa iyo inosimudzira yayo adamantane-se-sterically-inomanikidza chimiro..
Uku kugadziridzwa kunoshanda seine simba synergistic potentiator yeanxiolytic – nootropic compound Selank.
Inodzivirira varombo vaSelank ropa-uropi chipingamupinyi (BBB) kupinda, nokudaro kuwedzera central nervous system chiitiko cheAdalank zvakanyanya.
Kuwedzerwa kwe acetyl group inobvisa iyo yakanaka kubhadharisa yeN-terminal yemahara amino boka uye inoderedza iyo net charge ye peptide..
Iyi physicochemical inogadzirisa inogadzirisa iyo isoelectric point uye pamusoro pezvivakwa zveAdalank, kudzikisira kusanganisa kusingaite kwemagetsi.
Semagumo, Morekuru wemushonga unoyambuka chipingamupinyi cheropa-uropi zviri nyore uye unosvika pakati penheyo system.
Uyezve, acetylation inodzivirira Adalank kubva exopeptidase kudzikira uye inowedzera zvakanyanya mu vivo hafu yeupenyu.
Izvi zvinopa mukana wekurebesa kurapa mazinga eropa uye kunoderedza kazhinji dosing.
Kubatanidzwa kwe adamantane inogadzira yakagadzikana "conformation core" muAdalank peptide.
Izvi zvinopa yakagadziriswa nzvimbo yekutarisa kune iyo yekutanga inoshanduka mutsara peptide., kusimudzira stereochemical conformation inodiwa kune biological chiitiko kunyangwe iri mumamiriro ayo asina kusungwa.
Izvi zvinovandudza zvakanyanya kugona kwaAdalank kuyambuka iyo yeropa-brain barriers.
Pamusoro pe, Adalank inoratidza mamwe immunomodulatory mhedzisiro.
Kutevedzana
ac-thr-lys-pro-arg-pro-gly-pro-Adamanane-nh2
Nhamba yeCAS
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Molecular Formula
C46H75N13O10
Molecular Weight
970.19
Tsvakurudzo yeAdalank:
1.Nzira Yekuita
Efficacy-wise, Adalank's rigid chimiro chinowirirana zvakanyanya neiyo allosteric modulation nzvimbo ye GABA_A inogamuchira alpha subunit, kupa kwakasimba anxiolytic migumisiro.
Uyezve, iyo adamantane moiety inogonesa kusangana kwehydrophobic mu NMDA receptor chiteshi nzvimbo kusvika pakati nepakati calcium influx uye kudzivirira kubva kune excitotoxic kukuvara.
Ichi chivakwa chine mukana we neuroprotection mumhando dzekukuvara kwehuropi hwe ischemic uye post-traumatic stress disorder (PTSD).
2.Anxiolytic Migumisiro
Seyakagadziriswa inotorwa kubva kuSelank, Adalank inochengetedza hukama hwepamusoro-soro nebenzodiazepine saiti paGABA_A receptor α-subunit..
Zvisinei, iyo N-terminal acetylation uye adamantane scaffold shandura iyo yekusunga maitiro kubva "inochinjika induced fit” kuenda ku “rigid precise docking”.
Izvi zvinowedzera GABAergic inhibitory neurotransmission, kusimudzira chloride kupinda uye kukurumidza kudzikiswa kwechiitiko mu hyperactive amygdala-prefrontal cortex neural circuits..
Kusiyana ne benzodiazepines, Adalank inoratidza yakakwira receptor subtype selectivity, kugonesa kuchengetedzwa kwakasimba kweanxiolytic mhedzisiro pasina sedation, kuzorora kwemhasuru, kana kupindwa muropa nemishonga yechivanhu.
Zvayo therapeutic index ndizvo 3 ku 5 nguva dzakafara, kutsigira kwenguva refu-kutonga kwe generalized kusagadzikana kusagadzikana uye mamiriro ekuzvidya mwoyo kusagadzikana.
3.Cognitive Enhancement uye Memory Kuvandudza
Adalank inobudirira inhibisa kushandiswa kweNF-κB nzira yekuputika uye inowedzera BDNF mRNA kutaura by 50%-80% mu hippocampus.
Izvi zvinotungamira ku activation yezasi Akt/CREB nzira dzechiratidzo, kufambisa LTP induction uye kugadzirisa.
Iyo inovandudza zvakanyanya kuchengetedza ndangariro mukati kungonzvenga chete miedzo, inowedzera kudzidza kwenzvimbo mu Morris maze yemvura, uye zvinopesana scopolamine-induced cholinergic damage.
Preclinical data inoratidza kuti Adalank inoderedza kushanda ndangariro zvikanganiso ne 40%-60% uye kuderedza ndangariro dzechisikigo kuderera mumhuka dzakura, zvichiratidza kushanda mumatambudziko ekudzidza, nyoro yekuziva kukanganisa, uye kurangarira kwakabatana nezera kuderera.
4.Neuroprotective Migumisiro
Iyo adamantane chimiro muAdalank inotevedzera chiito che memantine, kuita semunhu asina makwikwi NMDA receptor anopikisa iyo inokonzeresa kuvharika-inotsamira kuvharika kwematanho akavhurika uye physiological regulation ye calcium influx..
Inoderedza pathological Ca²⁺ kupinda ne60–70% pasina kukanganisa physiological synaptic Ca²⁺ kusaina, kuwana yakasarudzika neuroprotective profile pasina kukanganisa zvakajairika basa.
Saka, preclinical zvidzidzo zvinoratidzira Adalank yakakosha yekushandura mukana wekupindira kwekutanga muakaoma sitiroko, kukuvara kwemusana, uye neurodegenerative zvirwere.
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