Inhibitor synthesis yog ib qho kev sib txuas tseem ceeb ntawm kev tsim qauv molecular thiab kev ua haujlwm kom pom tseeb, txhawm rau tsim cov khoom sib txuas nrog cov haujlwm tshwj xeeb thiab kev xaiv raws li cov qauv ua ntej. Nrog rau kev nce qib hauv cov organic hluavtaws chemistry, catalysis technology, thiab automated platforms, inhibitor synthesis tau hloov los ntawm ib txwm sim - thiab - yuam kev txoj kev mus rau ib tug qauv combining rational design thiab npaum npaj, muab ib tug ruaj khov thiab txhim khu kev qha molecular qhov chaw rau lub neej science kev tshawb fawb thiab kev siv tshuaj.
Tam sim no, inhibitor synthesis feem ntau siv ob txoj hauv kev: tag nrho cov synthesis thiab semi-synthesis. Tag nrho cov synthesis yog hais txog pib los ntawm cov khoom lag luam muaj cov khoom siv raw thiab maj mam tsim tag nrho cov pob txha pob txha thiab cov pab pawg ua haujlwm ntawm lub hom phiaj molecule los ntawm cov tshuaj lom neeg. Qhov kom zoo dua ntawm txoj kev no yog tias cov qauv tuaj yeem tsim tau tag nrho autonomously, tsis muaj kev txwv los ntawm cov khoom siv ntuj tsim, ua rau nws tsim tshwj xeeb rau kev tsim cov inhibitors nrog cov pob txha tshiab lossis kev hloov kho siab. Nyob rau hauv tag nrho cov txheej txheem synthesis, kev npaj ntawm cov tshuaj tiv thaiv kab mob yuav tsum xav txog cov txiaj ntsig, kev tswj hwm stereochemical, thiab kev tawm tsam sab nraud, feem ntau cuam tshuam nrog kev sib txuas lus (xws li Suzuki thiab Buchwald-Hartwig), condensation reactions, cyclization reactions, thiab tiv thaiv pab pawg cov tswv yim kom ua tiav kev sib dhos ntawm cov qauv nyuaj.
Semi-synthesis siv cov khoom ntuj lossis lawv cov khoom siv los ua cov khoom pib, qhia lossis hloov kho cov haujlwm tseem ceeb los ntawm kev hloov tshuaj lom neeg tsawg kom tau txais cov tshuaj inhibitors xav tau. Txoj kev no khaws cia qhov kev ua tau zoo thiab biocompatibility ntawm ntuj molecules thaum shortening txoj kev hluavtaws thiab txo cov nqi. Piv txwv li, rau qee qhov ntuj inhibitors uas muaj polyphenolic lossis terpene skeletons, hydrophilicity / hydrophobicity thiab lub hom phiaj khi cov khoom tuaj yeem hloov kho los ntawm kev xaiv oxidation, esterification, lossis amination cov tshuaj tiv thaiv. Tus yuam sij rau ib nrab-synthesis yog nyob rau hauv kev xaiv ntawm qhov chaw hloov kho hauv zos thiab kev tiv thaiv thiab kev tiv thaiv kev ua haujlwm ntawm cov pab pawg ua haujlwm siab kom tswj hwm qhov kev sib haum xeeb ntawm niam txiv molecule.
Nyob rau hauv xyoo tas los no, biocatalysis thiab synthetic biology txoj kev tau nce dav siv hauv inhibitor synthesis. Kev siv cov enzymes uas tsim los lossis tag nrho -cov kab ke ntawm tes rau kev xaiv catalysis tso cai rau kev hloov pauv tsis zoo los yog regiospecific uas nyuaj rau kev ua tiav raws li cov txheej txheem tshuaj ib txwm muaj nyob rau hauv cov mob me me, txhim kho cov khoom siv hluavtaws thiab txo cov khoom lag luam. Tsis tas li ntawd, khoom -theem synthesis plays lub luag haujlwm tseem ceeb hauv kev npaj peptide lossis oligonucleotide inhibitors, immobilizing loj hlob molecules ntawm kev txhawb nqa rau kev soj ntsuam sai thiab huv, ua rau nws tshwj xeeb tshaj yog tsim rau combinatorial chemistry tsev qiv ntawv tsim thiab siab -throughput optimization.
Hauv kev tsim cov tswv yim hluavtaws, nws tseem yuav tsum tau ua tib zoo xav txog cov kev npaj siv thiab ib puag ncig cov cai ntawm inhibitors. Piv txwv li, inhibitors siv hauv kev sim ntawm tes yuav tsum tau ua kom cov dej solubility zoo thiab daim nyias nyias permeability, thiab cov txheej txheem hluavtaws yuav tsum suav nrog cov pawg polar tsim los yog cov qauv tsim; inhibitors npaj rau ntev -lub sij hawm cia los yog kev kho mob siv yuav tsum tau optimize tshuaj stability thiab zam tau yooj yim hydrolyzed los yog photosensitive lug. Qhov ntsuab thiab scalability ntawm cov tshuaj tiv thaiv tej yam kev mob kuj tseem ceeb heev rau kev ntsuam xyuas cov kuab tshuaj pov tseg, txo zog noj, thiab txhim kho batch sib xws.
Zuag qhia tag nrho, cov txheej txheem inhibitor synthesis yog tsim los ntawm kev xaiv siab, kev hloov pauv, thiab kev ruaj khov. Tag nrho cov synthesis muab kev ywj pheej rau kev tsim kho tshiab, semi-synthesis khaws cov txiaj ntsig zoo ntawm natural synthesis, thiab biocatalysis muaj peev xwm tshiab rau cov txheej txheem me me thiab muaj txiaj ntsig zoo. Kev sib koom ua ke thiab iteration ntawm ntau lub thev naus laus zis tau txuas ntxiv txhim kho qhov zoo thiab ua haujlwm ntawm kev npaj inhibitor, tso cov khoom siv hauv paus rau kev cuam tshuam cov molecular.