Peptides o se vasega o mea faʻapipiʻi e fausia i le fesoʻotaʻiga o le tele o amino acids e ala i fusi peptide.E iai i soo se mea i mea ola.E oo mai i le taimi nei, e faitau sefulu afe peptide ua maua i mea ola.Peptides e iai sona sao taua i le faʻatonutonuina o gaioiga faʻatino o faiga eseese, okeni, masini ma sela ma i gaioiga o le olaga, ma e masani ona faʻaaogaina i suʻesuʻega faʻatino, suʻesuʻega o le antibody, atinaʻeina o vailaʻau ma isi matāʻupu.Faatasi ai ma le atinaʻeina o le biotechnology ma le peptide synthesis technology, o le tele ma le tele o vailaʻau peptide ua atiaʻe ma faʻaaogaina i le falemaʻi.
O loʻo i ai le tele o suiga o le peptide, lea e mafai ona vaevaeina naʻo le faʻaogaina o le pou ma le faʻagasologa o suiga (faʻaaogaina o le amino acid modification), ma le N-terminal modification, C-terminal modification, itu filifili filifili, amino acid modification, skeleton modification, ma isi, fa'alagolago i le nofoaga o suiga (Ata 1).I le avea ai o se auala taua e suia ai le fausaga o filifili autu poʻo vaega filifili vaega o filifili peptide, suiga peptide e mafai ona suia lelei le tino ma le kemikolo meatotino o peptide compounds, faateleina vai solubility, faaumiumi le taimi gaioiga i vivo, suia o latou tufatufaina o meaola, aveesea immunogenicity. , faʻaitiitia aʻafiaga oona, ma isi. I totonu o lenei pepa, o loʻo faʻaalia ai le tele o taʻiala mo suiga ole peptide ma o latou uiga.
1. Ta'amilosaga
Cyclic peptides e tele faʻaoga i le biomedicine, ma o le tele o peptides faʻanatura ma gaioiga faʻaola o peptides cyclic.Talu ai ona o peptides cyclic e foliga mai e sili atu le malosi nai lo peptides laina, latou te matua teteʻe i le faʻaogaina o meaʻai, e mafai ona ola i totonu o le vaega o meaʻai, ma faʻaalia ai se vavalalata malosi mo tali faʻatatau.O le cyclization o le auala sili lea ona tuusaʻo e faʻapipiʻi ai peptides cyclic, aemaise lava mo peptides e iai le auivi tetele.E tusa ai ma le faiga cyclization, e mafai ona vaevaeina i itu filifili filifili-itu itu ituaiga, terminal - itu itu ituaiga filifili, terminal - ituaiga terminal (itu i le ituaiga pito).
(1) filifili fa'a-fa'a-fa'a-fa'atasi
O le ituaiga sili ona taatele o le fa'ata'amilosaga o le filifili i le itu o le fa'asosooina o le disulfide i le va o toega o le cysteine.O lenei fa'ata'amilosaga e fa'ailoa mai e se pea o toega o le cysteine o lo'o fa'ate'aina ona fa'ama'i fa'ama'i e fai ai fusi fa'a-disulfide.Polycyclic synthesis e mafai ona ausia e ala i le aveeseina filifilia o vaega puipuia o le sulfhydryl.E mafai ona faia le cyclization a le o se soli-dissociation solvent po'o luga o se resin mua-dissociation.O le ta'amilosaga i luga o resini atonu e itiiti le aoga nai lo le so'o fa'ata'amilomilo ona o peptide o lo'o i resini e le faigofie ona fa'atupu fa'ata'amilomilo.O le isi ituaiga o itu-chain-side filifili cyclization o le fausia o se fausaga amide i le va o le aspartic acid po o le glutamic acid toega ma le faavae amino acid, lea e manaomia ai le vaega o le puipuiga o filifili filifili e tatau ona filifilia mai le polypeptide pe. i luga o le resini poʻo le maeʻa ona vavaeeseina.O le ituaiga lona tolu o le itu-chain - o le faʻasologa o filifili o le faʻavaeina o diphenyl ethers e tyrosine poʻo le p-hydroxyphenylglycine.O lenei ituaiga o uila i oloa faanatura e na'o mea e maua i meaola ninii, ma o oloa cyclization e masani ona i ai ni aoga faafomai.O le sauniuniga o nei mea faʻapipiʻi e manaʻomia ai tulaga faʻaalia uiga ese, o lea e le masani ona faʻaaogaina i le tuʻufaʻatasia o peptides masani.
(2) filifili fa'amau i le itu
O le faʻataʻavaleina o filifili pito i tua e masani ona aofia ai le C-terminal ma le vaega amino o le lysine poʻo le ornithine itu filifili, poʻo le N-terminal ma le aspartic acid poʻo le glutamic acid filifili itu.O isi polypeptide cyclization e faia e ala i le faia o sootaga eter i le va o laina C ma serine poʻo le threonine itu filifili.
(3) Ituaiga alalaupapa po'o le ulu-i-si'u
O polypeptides filifili e mafai ona fa'ata'amilomilo i se so'o pe fa'amauina i luga o se resini e ala i le ta'amilosaga o filifili.E tatau ona fa'aogaina le maualalo o peptides i le fa'aogaina o le solvent e aloese ai mai le oligomerization o peptides.Ole fua ole ulu-i-tail synthetic mama polypeptide e faalagolago ile faasologa ole filifili polypeptide.O le mea lea, aʻo leʻi saunia peptides cyclic i luga o se fua tele, e tatau ona faia muamua se faletusi o peptides taʻitaʻi filifili filifili muamua, sosoo ai ma le cyclization e suʻe ai le faasologa ma taunuuga sili.
2. N-methylation
O le N-methylation na tupu muamua i peptides masani ma ua faʻafeiloaʻi i le peptide synthesis e taofia ai le faʻavaeina o fusi o le hydrogen, ma faʻapea ona faʻamalosia atili ai peptides i le biodegradation ma le kilia.O le tuʻufaʻatasia o peptides e faʻaaoga ai N-methylated amino acid derivatives o le auala sili lea ona taua.E le gata i lea, o le tali a Mitsunobu o N-(2-nitrobenzene sulfonyl chloride) polypeptide-resin intermediates ma le methanol e mafai foi ona faʻaaogaina.O lenei metotia na faʻaaogaina e saunia ai faletusi peptide cyclic o loʻo i ai N-methylated amino acids.
3. Phosphorylation
O le Phosphorylation o se tasi o suiga sili ona taatele pe a maeʻa faʻaliliuga i le natura.I totonu o sela o le tagata, e sili atu i le 30% o polotini o loʻo phosphorylated.O le Phosphorylation, aemaise lava le phosphorylation toe faʻafoʻi, e iai sona sao taua i le puleaina o le tele o gaioiga feaveaʻi, e pei o le faʻaliliuina o faailoilo, faʻamatalaga o le kenera, taamilosaga o le cell ma le cytoskeleton regulation, ma apoptosis.
E mafai ona matauina le Phosphorylation i le tele o toega amino acids, ae o le sili ona taatele o le phosphorylation sini o serine, threonine, ma tyrosine toega.Phosphotyrosine, phosphothreonine, ma phosphoserine derivatives e mafai ona faʻafeiloaʻi i peptides i le taimi o le faʻasologa poʻo le faia pe a uma le peptide synthesis.E mafai ona ausia le phosphorylation filifilia i le faʻaaogaina o toega o le serine, threonine, ma le tyrosine lea e filifilia ai vaega puipuia.O nisi phosphorylation reagents e mafai foʻi ona faʻafeiloaʻi vaega o le phosphoric acid i totonu o le polypeptide e ala i le faʻasologa o pou.I tausaga talu ai nei, na ausia ai le phosphorylation faʻapitoa o le lysine i le faʻaaogaina o se vailaʻau Staudinger-phosphite tali (Ata 3).
4. Myristoylation ma palmitoylation
Acylation o le N-terminal ma gaʻo gaʻo e mafai ai peptides poʻo polotini e fusifusia i sela sela.O le myridamoylated sequence i luga o le N-terminal e mafai ai e Src aiga protein kinases ma faʻaliliuga transcriptase Gaq proteins e taulaʻi e fusifusia i sela sela.O le myristic acid na fesoʻotaʻi atu i le N-terminal o le resin-polypeptide e faʻaaoga ai faʻasalalauga masani, ma o le lipopeptide e maua mai e mafai ona vavae ese i lalo o tulaga masani ma faʻamamaina e le RP-HPLC.
5. Glycosylation
Glycopeptides pei o le vancomycin ma le teicolanin o vailaʻau taua mo le togafitia o faʻamaʻi siama faʻamaʻi, ma isi glycopeptides e masani ona faʻaaogaina e faʻaosofia ai le tino puipuia.E le gata i lea, talu ai o le tele o microbial antigens e glycosylated, e taua tele le suʻesuʻeina o glycopeptides mo le faʻaleleia o le togafitiga o faʻamaʻi pipisi.I le isi itu, ua maua ai o polotini i luga o le sela sela o sela tumo o loʻo faʻaalia ai le glycosylation faʻaletonu, lea e avea ai le glycopeptides ma se sao taua i le kanesa ma suʻesuʻega puipuiga puipuia.Glycopeptides e saunia e ala Fmoc / t-Bu.Glycosylated toega, e pei o le threonine ma serine, e masani ona faʻaofiina i polypeptides e pentafluorophenol ester faʻagaoioia fMOCs e puipuia glycosylated amino acids.
6. Isoprene
O le Isopentadienylation e tupu i luga o toega o le cysteine i le filifili pito lata ane i le C-terminal.O le protein isoprene e mafai ona faʻaleleia ai le fesoʻotaʻiga o le sela ma fausia ai le faʻaogaina o le protein-protein.O polotini ua fa'a-isopentadiena e aofia ai le tyrosine phosphatase, tama'i GTase, mole mole o le cochaperone, lamina faaniukilia, ma polotini fa'amau fa'atasi.Isoprene polypeptides e mafai ona saunia e faʻaaoga isoprene i resins poʻo le faʻaofiina o mea e maua mai ai le cysteine.
7. Suiga Polyethylene glycol (PEG).
E mafai ona fa'aoga le suiga ole PEG e fa'aleleia atili ai le mautu o le hydrolytic protein, biodistribution ma le solubility peptide.O le faʻaofiina o filifili PEG i peptides e mafai ona faʻaleleia atili a latou mea tau vailaʻau ma faʻalavelaveina foi le hydrolysis o peptides e enzymes proteolytic.PEG peptides e pasi atu i le glomerular capillary cross section sili atu ona faigofie nai lo peptides masani, e matua faʻaitiitia ai le kilia o fatu.Ona o le faʻalauteleina o le afa-ola o le PEG peptides i vivo, o le tulaga masani o togafitiga e mafai ona faʻatumauina i lalo ifo o tui ma faʻaitiitiga peptide vailaʻau.Ae ui i lea, o le suiga o le PEG e iai foʻi aʻafiaga leaga.Ole tele ole PEG e taofia ai le enzyme mai le fa'aleagaina o le peptide ma fa'aitiitia ai fo'i le fusifusia o le peptide i le tali fa'atatau.Ae o le PEG peptides 'maualalo affinity e masani lava ona faʻafefe e latou pharmacokinetic afa-ola umi, ma e ala i le i ai i totonu o le tino umi, o le PEG peptides e sili atu le avanoa e faʻafefe i totonu o masini faʻatatau.Ole mea lea, ole PEG polymer specifications e tatau ona sili ona lelei mo iuga sili ona lelei.I le isi itu, o le PEG peptides e faʻaputuina i totonu o le ate ona o le faʻaitiitia o le kilia o fatugaʻo, e mafua ai le macromolecular syndrome.O le mea lea, e manaʻomia le faʻatulagaina o suiga ole PEG pe a faʻaaogaina peptides mo suʻega vailaʻau.
O vaega masani o suiga ole PEG e mafai ona aoteleina e pei ona taua i lalo: Amino (-amine) -NH2, aminomethyl-Ch2-NH2, hydroxy-OH, carboxy-Cooh, sulfhydryl (-Thiol) -SH, Maleimide -MAL, succinimide carbonate - SC, succinimide acetate -SCM, succinimide propionate -SPA, n-hydroxysuccinimide -NHS, Acrylate-ch2ch2cooh, aldehyde -CHO (e pei o le propional-ald, butyrALD), faʻavae acrylic (-acrylate-acrl), azido-azide, biotinyl - Biotin, Fluorescein, glutaryl -GA, Acrylate Hydrazide, alkyne-alkyne, p-toluenesulfonate -OTs, succinimide succinate -SS, ma isi PEG derivatives ma carboxylic acids e mafai ona faʻapipiʻiina i n-terminal amines poʻo filifili lysine itu.Amino-activated PEG e mafai ona tu'u fa'atasi i le aspartic acid po'o le glutamic acid filifili itu.Mal-activated PEG e mafai ona tu'ufa'atasia i le mercaptan o filifili pito o le cysteine ua fa'amama atoatoa [11].E masani ona fa'avasegaina fa'asologa o PEG e fa'apea (fa'aaliga: mPEG o le methoxy-PEG, CH3O-(CH2CH2O)n-CH2CH2-OH):
(1) filifili sa'o PEG sui
mPEG-SC, mPEG-SCM, mPEG-SPA, mPEG-OTs, mPEG-SH, mPEG-ALD, mPEG-butyrALD, mPEG-SS
(2) suitulaga PEG e lua
HCOO-PEG-COOH, NH2-PEG-NH2, OH-PEG-COOH, OH-PEG-NH2, HCl·NH2-PEG-COOH, MAL-PEG-NHS
(3) fa'afesuia'i PEG lala
(mPEG)2-NHS, (mPEG)2-ALD, (mPEG)2-NH2, (mPEG)2-MAL
8. Biotinization
Biotin e mafai ona matua fusifusia i le avidin poʻo le streptavidin, ma o le malosi faʻamau e latalata i le fusi faʻatasi.O peptide e fa'aigoaina o le biotin e masani ona fa'aogaina ile immunoassay, histocytochemistry, ma le fluorescence-based flow cytometry.E mafai fo'i ona fa'aoga fa'ailoga antibiotin antibodies e fusifusia ai peptides biotinylated.E masani ona fa'apipi'i igoa o le biotin i le filifili itu o le lysine po'o le laina N.6-aminocaproic acid e masani ona faʻaaogaina e fai ma fusi i le va o peptides ma biotin.O le fusi e fetuutuunai i le fusifusia i le substrate ma sili atu ona fusifusia i le i ai o le faʻalavelave faʻafefe.
9. Fa'ailoga felanulanua'i
E mafai ona fa'aogaina le fa'ailoga o le fluorescent e su'e ai polypeptides i sela ola ma su'esu'e enzymes ma faiga o gaioiga.Tryptophan (Trp) e felanulanua'i, o lea e mafai ai ona fa'aoga mo le fa'ailoga fa'apitoa.Ole fuala'au fa'asao ole tryptophan e fa'alagolago ile si'osi'omaga lautele ma fa'aitiitia ile fa'aitiitia ole polarity solvent, ose meatotino e aoga mo le su'esu'eina o le fausaga o le peptide ma le fusifusia o le tali.Tryptophan fluorescence e mafai ona tineia e protonated aspartic acid ma glutamic acid, lea e mafai ona faatapulaaina lona faaaogaina.O le vaega o le Dansyl chloride (Dansyl) e matua'i fela'ua'i pe a fusifusia i se vaega amino ma e masani ona fa'aaogaina e fai ma fa'ailoga fa'amalama mo amino acids po'o polotini.
Fluorescence resonance Suiga malosi (FRET) e aoga mo suʻesuʻega enzyme.A fa'aogaina le FRET, o le polypeptide o le substrate e masani lava ona i ai se vaega fa'aigoa fa'amalama ma se vaega fa'ama'i.E tineia e le tineia le fa'aigoaina o vaega felanulanua'i e ala i le fa'aliliuina atu o le malosi e le-photon.A vavae ese le peptide mai le enzyme o loʻo fesiligia, o le vaega faʻailoga e faʻauluina le fluorescence.
10. Fale polypeptides
Cage peptides o lo'o i ai vaega puipuia e mafai ona aveese e puipuia ai le peptide mai le fusia i le tali.Pe a faʻaalia i le faʻamalama o le UV, e faʻagaoioia le peptide, toe faʻafoʻisia lona vavalalata i le tali.Talu ai e mafai ona pulea lenei faʻagaioiga faʻapitoa e tusa ai ma le taimi, amplitude, poʻo le nofoaga, e mafai ona faʻaogaina peptides fale e suʻesuʻe ai gaioiga o loʻo tutupu i sela.O vaega puipuia e sili ona fa'aaogaina mo polypeptides fale o 2-nitrobenzyl vaega ma a latou mea e maua mai ai, lea e mafai ona fa'aofiina i le peptide synthesis e ala i le puipuiga o le amino acid derivatives.Amino acid derivatives ua atiaeina o lysine, cysteine, serine, ma tyrosine.Aspartate ma glutamate derivatives, e ui i lea, e le masani ona faʻaaogaina ona o lo latou faʻaogaina i le cyclization i le taimi o le peptide synthesis ma le dissociation.
11. Polyantigenic peptide (MAP)
O peptide pupuu e masani lava e le puipuia ma e tatau ona tuʻufaʻatasia i polotini feaveaʻi e maua ai faʻamaʻi.Polyantigenic peptide (MAP) e aofia ai le tele o peptides tutusa e fesoʻotaʻi ma le lysine nuclei, lea e mafai ona faʻaalia faapitoa immunogens malosi ma e mafai ona faʻaoga e saunia ai peptide-carrier protein couplets.MAP polypeptides e mafai ona faʻapipiʻiina e ala i le faʻapipiʻiina o vaega malosi ile MAP resin.Ae ui i lea, o le le atoatoa o fesoʻotaʻiga e mafua ai ona misi pe tipiina filifili peptide i luga o nisi lala ma faʻapea e le faʻaalia ai meatotino o le uluai MAP polypeptide.I se isi itu, peptides e mafai ona saunia ma faʻamamā ese ma faʻapipiʻi i MAP.O le peptide sequence o loʻo faʻapipiʻi i le peptide core e faʻamalamalama lelei ma faigofie ona faʻaalia i le tele o spectrometry.
Fa'ai'uga
Suiga peptide o se auala taua o le mamanuina o peptides.O peptides fa'asolosolo fa'asolosolo e le gata e mafai ona fa'atumauina le maualuga o gaioiga fa'aletino, ae fa'apea fo'i ona aloese mai le fa'aletonu o le immunogenicity ma le toxicity.I le taimi lava e tasi, e mafai e le suiga o vailaʻau ona tuʻuina atu peptides ma nisi o mea sili ona lelei.I tausaga talu ai nei, o le auala o le CH activation mo le post-modification o polypeptides ua vave ona atiae, ma e tele taunuuga taua ua ausia.
Taimi meli: Mati-20-2023