
integraason

echuaivi-1 integrase ensaimine thadayunnathaayi theliyikkapetta oru anjjaatha fungazil ninnu verthirichedutha polycatide prakrithidatha ulppannamaanu integraason.
sambhavam.
thirichariyappedaatha oru anuvimukthamaaya fungazil integraason swaabhaavikamaayi sambhavikkunnu. eee fangasinu merck gaveshakar emf6836 enna label nalkiyittundu, koodaathe vermiculite adisthaanamaakkiyulla soolid media, eiii. dii 2 ll valarthi. sephadex elech 20 (cheria prakrithidatha uthppannangal verthirikkunnathinayi roopakalppana cheytha oru liqvid chromatography meediyam) leeii fungus valarchayude methyl ethyl keetton sathil jell permiyeshan chromatography uyarnna prakadanamulla liqvid chromatography integraasonine verthirikkaan pravarthippichu, ithu 1.8 gram/lii saandrathayil oru amophus podiyaayi verthirichu.
jaiva pravartthanangal.
hoost genomesil echuaivi provirusine samyojippikkunnathin utharavaadiyaaya vairal ensaimaaya echuaivi-1 integrasine integraason thadayunnu. 3-prime end prosessing, strand transfer prathikaranam enningane rund prathikaranangal upayogichaanu integrase ithu poortthiyaakkunnathu. eee rund prathikaranangalil aadyathethil, rund deoxynucleoducal neekkam cheythaanu vairal dna prosess cheiyunnathu. strand transfer prathikaranatthil, eee prosess cheytha 3-prime vairal dna attangal hoost chromosomal dnaumayi sahavarthithvathode bandhappettirikkunnu. 41 micrometer aisi 50 (pakuthi paramavadhi inhibittari concentration) upayogichu strand transfer prathikaranatthil edapedunnathiloode integraason echuaivi integrase pravartthanatthe thadayunnu.
uyarnna mutation nirakkum pradhana rogaprathirodha samvidaana koshangalude chittayaya unmoolanam kaaranam, echuaivi oru vaxine nirmmikkaan valare budhimuttulla oru vairasaanu. chila pareekshanangalil, pareekshanathmaka echuaivi waxinukal nalkia grouppukalkku yadhaarthathil placibo nalkia grouppukalekkaal echuaivi anubaadhayude saadhyatha kooduthalaanu. vairal rogangalkkethire pooraadunnathinulla parambaraagatha reethiyaaya prathirodha kuthivayppu pradhaanamaayum labhyamallathathinaal, chemotherapy oru mikacha oopshanaayi maarunnu. nirbhagyavashaal, echuaiviyude asaadhaaranamaaya uyarnna mutation nirakk manushyante rogaprathirodha samvidaanatheyum aanti-vairal marunnukalude phalatheyum ozhivakkaan athine vikasippikkaan anuvadikkunnu. ekkaaranathaal, echuaivikkethiraaya poraattam thudaraan puthiya aantivairal echuaivi-1 marunnukal aavasyamaanu. integraason upayogikkunna nishkriyamaakkal reethi athinte aathidheyathvathil echuaivi padaraathirikkaanulla vaagdaanam kaanikkunnu, ennirunnaalum ithu vairasine poornnamaayum illaathaakkilla.
synthesis.
pii-benzoquinoninteyum cyclopentadianinteyum saadhaaranayaayi labhyamaya dials-alder adakttil ninnu aarambhich integraasoninte motham laborattari synthesis thayyaaraakkiyittund. oru adisthaana madhyastha epoxidation prathikaranam upayogichu, ghadana 3 kaivarichu, ithu dbyuvinte saannidhyathil samagramaya hydroxymethylation sesham ghadana 4 lake nayichu. ghadana 4-nte roopeekaranam prathyekichum aakarshakamaan-ithu oru ghattathil rund pradhana sii-sii bondukal roopappeduthuka mathramalla, alavu varumaanathilum sambhavikkunnu. oru retro dials-alder prathikaranam upayogichu, ghadana 5 roopappettathu ekadesham alavu varumaanathilaan. 99 sathamaanam enantiomeric adhikathil roopappetta ghadana 6 nalkaan nischalamaaya lipace ps 30 ensime upayogichu oru ensaimatik traansterifikkeshan prakriyayiloode ghadana 5 disimmetrij cheythu.
praadhamika hydroxyl groupinteyum (kaarban 8) epoxide valayathinteyum (kaarban 4,5) dishaabodha phalangal kaaranam regioyum steeriyo selective aaya kuravaanu avasana integrason thanmaathrayile (3) kaarban 6 leeii hydroxyl grouppinte stereochemistry nirnnayikkunnath. kaarban 8-leeii hydroxy groupine pinneedu triethylisilil (tess) eedhar upayogichu samrabham nalkunnathinaayi thiranjeduttha reethiyil samrakshikkunnu. kaarban 1,2,8 ennivayile hydroxyl grouppukal samrakshikkappedunnu, thudarnnu kaarban 3-leeii carbonyl groupine stereoselective aayi kuraykkunnathu soodiyam borohydride upayogichu ghadana 9-ll chithreekarichirikkunna dial nalkunnu. eathenkilum ooksideshan prathikaranangal upayogikkunnathinu munbu, puthuthayi roopeekaricha rund hydroxyl grouppukale asattett esttarukalaayi samrakshikkukayum ghadana 10 roopappeduthukayum cheythu. kaarban 8 hydroxylile tess protecting groupine mattu grouppukalilonnum samrakshanam nalkaathe neekkam cheyyukayum thudarnnu kaarban 8 hydroxyl 11-ll kaanichirikkunna aldehyde nalkaan pisi upayogichu ooksidais cheyyukayum cheythu.
adutha ghattathil aldehyde carbonil (kaarban 8) oru hexile shringhala sthaapikkuka ulppedunnu. grignard riyejant hexilmagnesium bromide upayogichaanu ithu poortthiyaakkiyathu, ithu valare stereoselective aayirunnu-eee prathikaranam report cheiyunna rasathanthranjar avarude "santhosham" prakadippikkunnu. kaarban 8-nulla prathikaranatthil migrate cheiyunna kaarban 6-ll gadippichirikkunna asattett grouppinte directing swaadheenam moolamaanu uthppannam 12-nte eee steeriyoselektivitti ennu anumaanikkappedunnu. nirbhagyavashaal, uthppannathinte 42 sathamaanathil alkail cheyin sthaapichittilla, pakaram oru triasettett (ghadana 14) roopappeduthunnathinaayi anubandha asattett migreshanodoppam aldehyde kuranju. thapanilayum laayakavum maattaan sramichukondaanu sinthasisinte eee ghattam mechappeduthaanulla sramangal nadathiyathu. uyarnna thapanilayil, triasettett 14-ll kooduthal roopappettu, athesamayam kuranja thapanilayil prathikaranam mandagathiyilaayirunnu.
ghadana 12 taargett thanmathrayodu valare aduthaanu, 1-avasheshikkunnath 5 anga valayam adachu oru carbonyl undaakkuka maathramaan. sheshikkunna asattett samrakshana grouppukale neekkam cheyyaan bays hydrolysis upayogichu, athinte falamaayi ghadana 15 ll chithreekarichirikkunna tetrol. praadhamika hydroxyl grouppukalude ooksideshanum samyojitha electron cyclisation vazhi integraason (1) orotta ghattathil roopappedukayum ring roopappedukayum cheiyunnu, tempoy bleach upayogichu soodiyam klorait catalise cheiyunnu. samyojitha electrocyclic prathikaranavum carbonyl roopeekaranavum vishadeekarikkaan nirddeshichittulla oru parivartthana avasthayaanu structure 16.

