Peptide nicyiciro cyimvange zakozwe muguhuza aside amine nyinshi binyuze mumigozi ya peptide.Biragaragara hose mubinyabuzima bizima.Kugeza ubu, ibihumbi icumi bya peptide byabonetse mu binyabuzima.Peptide igira uruhare runini muguhuza ibikorwa byimikorere ya sisitemu zitandukanye, ingingo, ingirangingo ningirabuzimafatizo ndetse no mubikorwa byubuzima, kandi akenshi bikoreshwa mugusesengura imikorere, ubushakashatsi bwa antibody, guteza imbere ibiyobyabwenge nizindi nzego.Hamwe niterambere ryikoranabuhanga ryibinyabuzima na peptide synthesis, imiti myinshi ya peptide yatejwe imbere kandi ikoreshwa mubuvuzi.
Hariho uburyo butandukanye bwo guhindura peptide, bushobora kugabanywa gusa muburyo bwo guhindura no guhindura inzira (ukoresheje aminide acide ikomoka), hamwe na N-terminal, C-terminal, guhindura urunigi, guhindura aside amine, guhindura skeleton, n'ibindi, ukurikije urubuga rwo guhindura (Ishusho 1).Nuburyo bwingenzi bwo guhindura imiterere yuruhererekane cyangwa amatsinda yuruhererekane rwurunigi rwurunigi rwa peptide, guhindura peptide birashobora guhindura neza imiterere yumubiri nubumara byimiti ya peptide, kongera amazi, kongera igihe cyibikorwa muri vivo, guhindura ikwirakwizwa ryibinyabuzima, gukuraho ubudahangarwa bw'umubiri , kugabanya ingaruka zuburozi, nibindi. Muri iyi nyandiko, ingamba nyinshi zingenzi zo guhindura peptide nibiranga.
1. Amagare
Peptide ya cycle ifite porogaramu nyinshi muri biomedicine, kandi peptide nyinshi zifite ibikorwa byibinyabuzima ni peptide ya cyclic.Kuberako peptide ya cyclicique ikunda gukomera kuruta peptide yumurongo, irwanya cyane sisitemu yumubiri, irashobora kubaho mumyanya yumubiri, kandi ikagaragaza isano ikomeye kubakira.Kuzunguruka ni inzira itaziguye yo guhuza peptide ya cyclicale, cyane cyane kuri peptide ifite skeleton nini yubatswe.Ukurikije uburyo bwo kuzenguruka, birashobora kugabanywa muburyo bwuruhererekane rwuruhande rwuruhererekane, itumanaho - ubwoko bwuruhererekane, itumanaho - ubwoko bwanyuma (ubwoko bwanyuma).
(1) kuruhande-kuruhande
Ubwoko busanzwe bwuruhererekane rwuruhande rwuruhererekane ni ukuzuza disulfide hagati y ibisigazwa bya sisitemu.Uku kuzunguruka gutangizwa nibisigisigi bya sisitemu byangiritse hanyuma bigahinduka okiside kugirango bibe inkwano ya disulfide.Synthesis ya polycyclic irashobora kugerwaho mugukuraho guhitamo amatsinda yo kurinda sulfhydryl.Kuzunguruka birashobora gukorwa haba mumashanyarazi nyuma yo gutandukana cyangwa kumurongo wabanjirije gutandukana.Kuzunguruka ku bisigazwa birashobora kuba bike cyane kuruta kuzunguruka kwizuba kuko peptide kumisozi ntabwo byoroshye guhuza ibizunguruka.Ubundi bwoko bwuruhererekane - uruziga rwuruhande rwuruziga ni ugukora imiterere ya amide hagati ya acide ya aspartic cyangwa glutamic aside isigara hamwe na aside amine fatizo, bisaba ko itsinda ririnda urunigi rugomba gushobora gukurwa muburyo bwa polypeptide. kuri resin cyangwa nyuma yo gutandukana.Ubwoko bwa gatatu bwuruhererekane - uruziga rwuruhande rwikurikiranya ni ugukora diphenyl ethers na tyrosine cyangwa p-hydroxyphenylglycine.Ubu bwoko bwa cycle mubicuruzwa bisanzwe biboneka gusa mubicuruzwa bya mikorobe, kandi ibicuruzwa byizunguruka bifite agaciro k'imiti.Gutegura ibyo bikoresho bisaba uburyo bwihariye bwo kubyitwaramo, ntabwo rero bikoreshwa kenshi muguhuza peptide isanzwe.
(2) itumanaho-kuruhande
Urunigi rwuruhande rwuruziga rusanzwe rurimo C-terminal hamwe nitsinda rya amino ryurunigi rwa lysine cyangwa ornithine, cyangwa N-terminal hamwe na acide ya aspartic cyangwa glutamic aside urunigi.Ubundi polypeptide cycleisation ikorwa mugukora ether ihuza itumanaho C na serine cyangwa iminyururu ya threonine.
(3) Ubwoko bwa Terminal cyangwa umutwe-umurizo
Urunigi polypeptide irashobora kuzunguruka mumashanyarazi cyangwa igashyirwa kumurongo ukoresheje uruziga.Ubwinshi bwa peptide bugomba gukoreshwa muguhuza solvent kugirango wirinde oligomerisiyumu ya peptide.Umusaruro wumutwe-umurizo synthique impeta polypeptide biterwa nurukurikirane rwa polypeptide.Kubwibyo, mbere yo gutegura peptide ya cyclicale ku nini nini, hagomba kubanza gushingwa isomero rya peptide ishobora kuba ifunze umunyururu, hanyuma hagakurikiraho kuzunguruka kugirango ubone urutonde hamwe nibisubizo byiza.
2. N-methylation
N-methylation yabanje kugaragara muri peptide karemano kandi yinjizwa muri synthesis ya peptide kugirango hirindwe ko habaho imiyoboro ya hydrogène, bityo bigatuma peptide irwanya biodegradation no kwera.Synthesis ya peptide ukoresheje N-methylated amino acide ni uburyo bwingenzi.Hiyongereyeho, reaction ya Mitsunobu ya N- (2-nitrobenzene sulfonyl chloride) polypeptide-resin ihuza na methanol nayo irashobora gukoreshwa.Ubu buryo bwakoreshejwe mugutegura amasomero ya cyclic peptide arimo aside N-methylated amino acide.
3. Fosifora
Fosifora ni kimwe mubisanzwe byahinduwe nyuma yubusobanuro muri kamere.Mu ngirabuzimafatizo z'abantu, poroteyine zirenga 30% zifite fosifori.Fosifora, cyane cyane fosifora ihindagurika, igira uruhare runini mugucunga inzira nyinshi zingirabuzimafatizo, nko guhererekanya ibimenyetso, imvugo ya gene, ingirabuzimafatizo no kugenzura cytoskeleton, na apoptose.
Fosifora irashobora kugaragara ku bisigazwa bitandukanye bya aside amine, ariko intego ya fosifora ikunze kugaragara ni serine, threonine, hamwe na tirozine.Fosifotirosine, fosiforeyonine, hamwe na fosifosine ikomoka kuri fosifoserine irashobora kwinjizwa muri peptide mugihe cya synthesis cyangwa ikorwa nyuma ya synthesis ya peptide.Fosifora ihitamo irashobora kugerwaho ukoresheje ibisigisigi bya serine, threonine, na tyrosine bikuraho guhitamo amatsinda arinda.Imiti imwe ya fosifora irashobora kandi kwinjiza amatsinda ya aside ya fosifori muri polypeptide muguhindura inyandiko.Mu myaka yashize, urubuga rwihariye rwa fosifora ya lysine rwagezweho hifashishijwe imiti yatoranijwe ya Staudinger-fosifite (Ishusho 3).
4. Myristoylation na palmitoylation
Acylation ya N-terminal hamwe na aside irike ituma peptide cyangwa proteyine zihuza na selile.Urutonde rwa myridamoylated kuri N-terminal ituma Src yumuryango wa protein kinase hamwe na transcriptase ya Gaq proteyine zigamije guhuza na selile.Acide Myristic yahujwe na N-terminal ya resin-polypeptide ikoresheje uburyo busanzwe bwo guhuza, kandi ibisubizo bya lipopeptide bishobora gutandukana mubihe bisanzwe kandi bigasukurwa na RP-HPLC.
5. Glycosylation
Glycopeptides nka vancomycine na teicolanine ni antibiyotike y'ingenzi mu kuvura indwara ziterwa na bagiteri zidakira imiti, kandi izindi glycopeptide zikoreshwa kenshi mu gukingira umubiri.Byongeye kandi, kubera ko antigene nyinshi za mikorobe zifite glycosilated, ni ngombwa cyane kwiga glycopeptides kugirango tunonosore ingaruka zo kuvura indwara.Ku rundi ruhande, byagaragaye ko poroteyine ziri mu ngirabuzimafatizo z'uturemangingo tw’ibibyimba zigaragaza glycosylation idasanzwe, bigatuma glycopeptide igira uruhare runini mu bushakashatsi bwa kanseri ndetse no kwirinda indwara.Glycopeptides itegurwa nuburyo bwa Fmoc / t-Bu.Ibisigazwa bya Glycosylated, nka threonine na serine, bikunze kwinjizwa muri polypeptide na pentafluorophenol ester ikora fMOCs kugirango irinde aside aside ya glycosilated.
6. Isoprene
Isopentadienylation iboneka ku bisigazwa bya sisitemu mumurongo wuruhande hafi ya C-terminal.Poroteyine isoprene irashobora guteza imbere ingirabuzimafatizo no gukora poroteyine.Intungamubiri za Isopentadienated zirimo fosifata ya tyrosine, GTase nto, molekile ya cochaperone, lamina ya kirimbuzi, hamwe na poroteyine zihuza centromeric.Isoprene polypeptide irashobora gutegurwa ukoresheje isoprene kumurongo cyangwa mugutangiza ibikomoka kuri sisitemu.
7. Guhindura polyethylene glycol (PEG)
Guhindura PEG birashobora gukoreshwa mugutezimbere hydrolytike ya protein, gukwirakwiza ibinyabuzima hamwe na peptide solubile.Kwinjiza iminyururu ya PEG kuri peptide birashobora kunoza imiterere ya farumasi kandi bikanabuza hydrolysis ya peptide na enzymes za proteolyique.PEG peptide inyura muri glomerular capillary cross cross byoroshye kuruta peptide isanzwe, bigabanya cyane impyiko.Bitewe nigihe kinini cyubuzima bwa peptide ya PEG muri vivo, urwego rusanzwe rwo kuvura rushobora kugumaho hamwe na dosiye nkeya hamwe nibiyobyabwenge bya peptide bidakunze kubaho.Ariko, guhindura PEG nabyo bigira ingaruka mbi.Umubare munini wa PEG urinda enzyme kwangiza peptide kandi ikanagabanya guhuza peptide guhuza reseptor.Ariko PEG peptide idafitanye isano nubusanzwe irarangizwa nigihe kirekire cyubuzima bwa farumasi, kandi mugihe uhari mumubiri igihe kirekire, peptide ya PEG ifite amahirwe menshi yo kwinjizwa mumitsi.Kubwibyo, PEG polymer ibisobanuro bigomba kuba byiza kubisubizo byiza.Ku rundi ruhande, peptide ya PEG irundanya mu mwijima bitewe no kugabanuka kw'impyiko, bikaviramo syndrome ya macromolecular.Kubwibyo, guhindura PEG bigomba gutegurwa neza mugihe peptide ikoreshwa mugupima ibiyobyabwenge.
Amatsinda asanzwe ahindura abahindura PEG arashobora kuvunagurwa muburyo bukurikira: Amino (-amine) -NH2, aminomethyl-Ch2-NH2, hydroxy-OH, carboxy-Cooh, sulfhydryl (-Thiol) -SH, Maleimide -MAL, karubone ya succinimide - SC, succinimide acetate -SCM, propionate ya succinimide -SPA, n-hydroxysuccinimide -NHS, Acrylate-ch2ch2cooh, aldehyde -CHO (nka propional-ald, butyrALD), ishingiro rya acrylic (-acrylate-acrl), azido-azide Biotin, Fluorescein, glutaryl -GA, Acrylate Hydrazide, alkyne-alkyne, p-toluenesulfonate -OTs, succinimide succinate -SS, nibindi.PEG ikora Amino irashobora guhuzwa na acide aspartic cyangwa glutamic aside iminyururu.PEG ikora nabi irashobora guhuzwa na mercaptan yumunyururu wa sisitemu wangiritse rwose [11].Abahindura PEG mubisanzwe bashyizwe muburyo bukurikira (icyitonderwa: mPEG ni mikorerexy-PEG, CH3O- (CH2CH2O) n-CH2CH2-OH):
(1) urunigi rugororotse PEG uhindura
mPEG-SC, mPEG-SCM, mPEG-SPA, mPEG-OTs, mPEG-SH, mPEG-ALD, mPEG-butyrALD, mPEG-SS
(2) guhindura imikorere ya PEG
HCOO-PEG-COOH, NH2-PEG-NH2, OH-PEG-COOH, OH-PEG-NH2, HCl · NH2-PEG-COOH, MAL-PEG-NHS
(3) ishami rya PEG uhindura
(mPEG) 2-NHS, (mPEG) 2-ALD, (mPEG) 2-NH2, (mPEG) 2-MAL
8. Ibinyabuzima
Biotine irashobora guhambirwa cyane na avidin cyangwa streptavidin, kandi imbaraga zo guhuza ziba hafi yubusabane bwa covalent.Peotide ya biotine ikoreshwa cyane muri immunoassay, histocytochemie, hamwe na fluorescence ishingiye kuri flux cytometrie.Antibodiyite za antibiotine zirashobora kandi gukoreshwa muguhuza peptide ya biotinylated.Ibirango bya Biotin akenshi bifatanye kumurongo wa lysine cyangwa N terminal.Acide 6-aminocaproic ikoreshwa kenshi nkumubano hagati ya peptide na biotine.Inkunga iroroshye guhuza substrate kandi ihuza neza imbere yimbogamizi zidasanzwe.
9. Ikimenyetso cya Fluorescent
Ikimenyetso cya Fluorescent kirashobora gukoreshwa mugukurikirana polypeptide mungingo ngengabuzima no kwiga enzymes hamwe nuburyo bwo gukora.Tryptophan (Trp) ni fluorescent, irashobora rero gukoreshwa mubirango byimbere.Ibyuka bihumanya bya tripitofani biterwa nibidukikije bya peripheri kandi bigabanuka hamwe no kugabanuka kwa polarite ikabije, umutungo ufite akamaro mukumenya imiterere ya peptide no guhuza reseptor.Tryptophan fluorescence irashobora kuzimwa na acide protartique acide na acide glutamic, ishobora kugabanya ikoreshwa ryayo.Itsinda rya Dansyl chloride (Dansyl) ni fluorescent cyane iyo ihujwe nitsinda rya amino kandi ikoreshwa kenshi nka label ya fluorescent ya aside amine cyangwa proteyine.
Fluorescence resonance Guhindura ingufu (FRET) ni ingirakamaro kubushakashatsi bwa enzyme.Iyo FRET ishyizwe mubikorwa, substrate polypeptide mubisanzwe iba irimo itsinda rya fluorescence hamwe nitsinda rya fluorescence.Amatsinda yanditseho fluorescent azimya nu kuzimya binyuze mu kohereza ingufu zitari fotone.Iyo peptide itandukanijwe na enzyme ivugwa, itsinda ryirango risohora fluorescence.
10. Cage polypeptides
Cage peptide ifite amatsinda arinda gukururwa arinda peptide guhambira reseptor.Iyo ihuye nimirasire ya UV, peptide irakora, igasubirana na reseptor.Kuberako iyi optique ikora ishobora kugenzurwa ukurikije igihe, amplitude, cyangwa ahantu, peptide ya cage irashobora gukoreshwa mukwiga reaction ziba muri selile.Amatsinda akoreshwa cyane kurinda cage polypeptide ni amatsinda 2-nitrobenzyl hamwe ninkomoko yabyo, ashobora kwinjizwa muri synthesis ya peptide akoresheje aside irinda aside amine.Ibikomoka kuri aside Amino byakozwe ni lysine, sisitemu, serine, na tirozine.Ibikomoka kuri Aspartate na glutamate, ariko, ntibisanzwe bikoreshwa bitewe nuburyo bworoshye bwo kuzunguruka mugihe cya peptide synthesis no gutandukana.
11. Peptide ya polyantigenic (MAP)
Peptide ngufi mubisanzwe ntabwo ikingira kandi igomba guhuzwa na poroteyine zitwara kugirango zivemo antibodi.Peptide ya polyantigenic (MAP) igizwe na peptide nyinshi ihuye na lysine nuclei, ishobora kwerekana cyane cyane immunogène nyinshi kandi ishobora gukoreshwa mugutegura peptide-itwara proteine.MAP polypeptide irashobora guhuzwa na synthesis ikomeye ya synthesis kuri MAP resin.Ariko, guhuza kutuzuye bivamo kubura cyangwa kugabanya iminyururu ya peptide kumashami amwe bityo ntigaragaza imiterere ya polypeptide yambere ya MAP.Nubundi buryo, peptide irashobora gutegurwa no kwezwa ukwayo hanyuma igahuzwa na MAP.Urutonde rwa peptide rwometse kuri peptide rwasobanuwe neza kandi rworoshe kurangwa na mass spectrometrie.
Umwanzuro
Guhindura peptide nuburyo bwingenzi bwo gukora peptide.Peptide yahinduwe mumiti ntishobora gukomeza ibikorwa byibinyabuzima gusa, ariko kandi irinda neza ingaruka ziterwa nubudahangarwa nuburozi.Mugihe kimwe, guhindura imiti birashobora guha peptide hamwe nibintu bishya byiza.Mu myaka yashize, uburyo bwo gukora CH kugirango nyuma yo guhindura polypeptide bwatejwe imbere byihuse, kandi ibisubizo byinshi byingenzi byagezweho.
Igihe cyo kohereza: Werurwe-20-2023