Thiostreptonyog ib yam khoom uas tsis tshua muaj kab mob uas yog siv los ua tshuaj pleevVeterinary tshuaj tua kab mobthiab kuj muaj cov tshuaj tiv thaiv kab mob zoo thiab tiv thaiv qog noj ntshav. Tam sim no, nws yog kiag li chemically synthesized.
Thiostrepton, thawj zaug cais tawm ntawm cov kab mob hauv xyoo 1955, muaj cov tshuaj tua kab mob txawv txawv: nws inhibits protein biosynthesis los ntawm kev khi rau ribosomal RNA thiab nws cov proteins uas cuam tshuam. Dorothy Crowfoot Hodgkin, tus kws tshaj lij Askiv Askiv thiab tus yeej Nobel nqi zog xyoo 1964, nrhiav pom tus qauv hauv xyoo 1970.
Thiostrepton muaj 10 rings, 11 peptide daim ntawv cog lus, uas nws kim heev unsaturation, thiab 17 stereocenters. Txawm tias qhov nyuaj tshaj yog qhov tseeb tias nws yog rhiab heev rau acids thiab bases. Nws yog leej niam leej txiv compound thiab cov tswv cuab complex ntawm thiopeptide tshuaj tua kab mob tsev neeg.
Tam sim no qhov sib xyaw no tau ua tiav rau kev hais lus qab zib ntawm chemistry xibfwb KS Nicolaou thiab nws cov npoj yaig los ntawm Scripps Research Institute thiab University of California ntawm San Diego [Angew. Chem. kev thoob ntiaj teb. Editors, 43, 5087 thiab 5092 (2004)].
Christopher J. Moody, Senior Research Fellow nyob rau hauv Department of Chemistry ntawm University of Exeter, UK, tau hais tias: "Qhov no yog ib qho kev sib xyaw ua ke thiab kev ua tiav zoo kawg nkaus los ntawm pawg Nicolaou." doxorubicin D.
Ntsiab rau cov qauv ntawmTHIOSTREPTONyog lub nplhaib dehydropiperidine, uas txhawb nqa didehydroalanine tus Tsov tus tw thiab ob lub macrocycles - 26-tus tswvcuab thiazoline-muaj nplhaib thiab 27-tus tswvcuab quinalcolic acid system. Nicolaou thiab cov npoj yaig tsim lub nplhaib dehydropiperidine tseem ceeb los ntawm cov ntaub ntawv pib yooj yim siv biomimetic iso-Diels-Alder dimerization cov tshuaj tiv thaiv. Cov kauj ruam tseem ceeb no tau pab lees paub qhov kev pom zoo xyoo 1978 uas cov kab mob siv cov tshuaj tiv thaiv biosynthesize thiopeptide tshuaj tua kab mob.
Nicolaou thiab cov npoj yaig tau koom nrog dehydropiperidine rau hauv thiazoline-muaj macrocycle. Lawv ua ke no macrocycle nrog ib tug qauv uas muaj quinalcolic acid thiab ib tug didehydroalanine tail precursor. Tom qab ntawd lawv tau ntxuav cov khoom kom tau txaisthiostrepton ua.
Cov kws tshuaj xyuas ntawm pab pawg ob cov ntaub ntawv hais tias qhov kev sib txuas "yog ib qho txuj ci uas qhia txog cov thev naus laus zis hauv lub xeev thiab qhib lub qab ntug tshiab rau kev tshawb fawb muaj txiaj ntsig rau hauv cov qauv, kev ua, thiab kev ua haujlwm."
Post lub sij hawm: Oct-31-2023