Ib qho polypeptide yog ib qho chaw tsim los ntawm ob lossis ntau dua amino acids txuas los ntawm peptide bonds (amide bonds). Polypeptides ua lub luag haujlwm tseem ceeb hauv kev tswj hwm kev ua haujlwm ntawm ntau lub cev, lub cev, cov ntaub so ntswg, thiab cov hlwb hauv lub cev, thiab nquag siv hauv kev tshuaj xyuas kev ua haujlwm, kev tshawb fawb tshuaj tiv thaiv, thiab kev tsim tshuaj. Hloov kho polypeptides los hloov lawv cov khoom siv physicochemical yog ib qho txheej txheem hauv kev tshawb fawb polypeptide. Cov kev hloov kho polypeptide muaj ntau haiv neeg, thiab raws li qhov chaw hloov kho, lawv tuaj yeem muab faib ua N- cov kev hloov pauv hauv lub davhlau ya nyob twg, C- kev hloov kho lub davhlau ya nyob twg, kev hloov pauv ntawm cov saw hlau, cov kev hloov pauv amino acid, thiab kev hloov kho pob txha (Daim duab 1). Raws li ib qho tseem ceeb ntawm kev hloov cov qauv saw tseem ceeb lossis cov pab pawg ntawm cov peptides, kev hloov kho polypeptide tuaj yeem hloov pauv cov khoom siv ntawm cov tshuaj peptide, ua kom cov dej solubility, hloov lawv cov biodistribution, ncua sij hawm vivo lub sij hawm, txo cov kev mob tshwm sim, thiab tshem tawm cov immunogenicity. Niaj hnub no, peb yuav qhia txog qee qhov tseem ceeb tshaj plaws kev hloov kho polypeptide thiab lawv cov yam ntxwv.
1. Cyclation
Nyob rau hauv qhov xwm txheej, ntau yam khoom siv roj ntsha polypeptides yog cyclic polypeptides; Yog li ntawd, cyclic peptides muaj ntau daim ntawv thov nyob rau hauv niaj hnub biomedicine. Cyclic peptides, piv rau linear peptides, muaj kev rigidity zoo dua thiab muaj zog heev rau lub plab zom mov, yog li tso cai rau lawv kom ciaj sia nyob rau hauv lub plab zom mov thiab muaj zog affinity rau lub hom phiaj receptors. Cyclic peptides feem ntau yog tsim los ntawm cyclization, uas tuaj yeem muab faib ua sab - saw - mus rau - sab - saw, davhlau ya nyob twg - mus rau - sab - saw, thiab lub davhlau ya nyob twg - mus rau {{10}{10} . txuas txoj kev cyclization.
(1) Sab - saws - mus rau - sab - saw cyclization
Disulfide bridging ntawm cysteine residues yog ib txoj hauv kev zoo tshaj plaws los tsim peptide rings, thiab txoj kev no belongs rau sab - saw - mus rau - sab - saw cyclization. Qhov no cyclization yog qhia los ntawm deprotecting ib khub ntawm cysteine residues thiab ces oxidizing lawv los ua ib tug disulfide daim ntawv cog lus. Polycyclic synthesis tuaj yeem ua tiav los ntawm kev xaiv tshem tawm thiol tiv thaiv pawg. Cyclization tuaj yeem ua tau nyob rau hauv cov kuab tshuaj tom qab dissociation los yog ntawm cov resin ua ntej dissociation. Txij li thaum peptides ntawm resin tsis yooj yim tsim cyclizable conformations, cyclization ntawm resin tej zaum yuav tsawg npaum li cyclization hauv hnyav. Hom thib ob ntawm sab- saw- sab- saw cyclization cuam tshuam nrog kev tsim cov qauv amide ntawm aspartic acid lossis glutamic acid residues thiab cov amino acid yooj yim. Qhov no xav kom cov pab pawg tiv thaiv ntawm cov saw hlau sab yuav tsum tau xaiv tshem tawm, ob qho tib si ntawm cov resin thiab tom qab dissociation. Hom thib peb ntawm sab- saw- sab- saw cyclization cuam tshuam nrog kev tsim ntawm biphenyl ether los ntawm tyrosine los yog p-hydroxyphenylglycine; Txawm li cas los xij, kev npaj ntawm cov tebchaw no yuav tsum muaj cov tshuaj tiv thaiv tshwj xeeb thiab yog li tsis nquag siv hauv kev sib xyaw ntawm cov pa peptides.
(2) Terminal - mus rau - sab saw
Terminal -rau- sab saw cyclization feem ntau cuam tshuam nrog kev tsim ntawm amide daim ntawv cog lus ntawm C-terminus thiab cov amino pawg ntawm lysine lossis ornithine sab saw, lossis nruab nrab ntawm N-terminus thiab aspartic lossis glutamic acid sab saw. Qee qhov peptide cyclizations kuj yog tsim los ntawm kev tsim ntawm ether daim ntawv cog lus ntawm lub davhlau ya nyob twg C-terminus thiab serine lossis threonine sab saw.
(3) Lub taub hau- mus rau -tail (los yog davhlau ya nyob twg-terminal) cyclization yog tsim los ntawm midation ntawm N-terminal amino pawg thiab C-terminal carboxyl pawg ntawm peptide. Cov saw hlau-zoo li peptides tuaj yeem raug cyclized hauv cov kuab tshuaj los yog immobilized ntawm cov resin ntawm sab- chain cyclization. Cyclation hauv cov kuab tshuaj yuav tsum tau ua los ntawm kev siv cov peptides tsawg kom tsis txhob oligomerization. Cov txiaj ntsig ntawm lub taub hau-rau-tail saw synthesis ntawm cyclic peptides nyob ntawm seb qhov sib lawv liag ntawm cov saw peptide. Yog li ntawd, ua ntej loj -kev npaj ntawm cyclic peptides, ib lub tsev qiv ntawv ntawm cov saw hlau lead peptides yuav tsum xub tsim, tom qab ntawd los ntawm cyclization kom pom cov kab ke uas tau txais txiaj ntsig zoo tshaj plaws.
2. Glycosylation
Peb cov glycopeptides ntau tshaj plaws, xws li vancomycin thiab teicoplanin, yog cov tshuaj tua kab mob tseem ceeb rau kev kho tshuaj - tiv thaiv kab mob. Lwm cov glycopeptides feem ntau yog siv los txhawb kev tiv thaiv kab mob. Tsis tas li ntawd, txij li ntau cov kab mob microbial antigens yog glycosylated, kev kawm glycopeptides yog qhov tseem ceeb rau kev txhim kho kev kho mob ntawm cov kab mob. Ntawm qhov tod tes, cov kev tshawb fawb tau pom tias cov proteins ntawm cov cell membranes ntawm cov qog nqaij hlav muaj qhov txawv txav ntawm glycosylation, ua rau glycopeptides ua lub luag haujlwm tseem ceeb hauv kev tshawb nrhiav qog nqaij hlav thiab kev tiv thaiv qog noj ntshav. Kev npaj glycopeptide feem ntau siv Fmoc/t-Bu txoj kev. Glycosylated residues, xws li threonine thiab serine, feem ntau nkag mus rau hauv peptides ntawm Fmoc tiv thaiv qhib los ntawm pentafluorophenol esters.
3. Phosphorylation
Hauv tib neeg lub hlwb, ntau dua 30% ntawm cov proteins yog phosphorylated. Phosphorylation, tshwj xeeb tshaj yog thim rov qab phosphorylation, plays lub luag haujlwm tseem ceeb hauv kev tswj ntau cov txheej txheem ntawm tes, xws li cov teeb liab hloov, kev qhia cov noob, lub voj voog ntawm tes thiab kev tswj hwm cytoskeleton, thiab apoptosis.
Phosphorylation tuaj yeem pom ntawm ntau yam ntawm cov amino acid residues, tab sis feem ntau cov hom phiaj phosphorylation yog serine, threonine, thiab tyrosine residues. Phosphotyrosine, phosphothreonine, thiab phosphoserine derivatives tuaj yeem nkag mus rau hauv peptides thaum lub sijhawm ua ke lossis tsim tom qab-synthesis. Kev xaiv phosphorylation tuaj yeem ua tiav siv serine, threonine, thiab tyrosine residues nrog kev xaiv tshem tawm ntawm pab pawg tiv thaiv. Qee cov tshuaj phosphorylating kuj tseem tuaj yeem qhia phosphate pawg rau hauv peptides los ntawm kev hloov kho tom qab-. Tsis ntev los no, muaj xwm txheej ntawm qhov chaw- tshwj xeeb phosphorylation ntawm lysine siv cov tshuaj Chemoselective Staudinger-phosphite cov tshuaj tiv thaiv.
