Peptides ikirasi yemakomponi akaumbwa nekubatana kweamino acids akawanda kuburikidza ne peptide bond.Dzinowanikwa pose pose muzvinhu zvipenyu.Kusvika zvino, makumi ezviuru zvemapeptide akawanikwa mune zvipenyu.Peptides inoita basa rakakosha mukugadzirisa mabasa anoshanda eakasiyana masisitimu, nhengo, matishu uye maseru uye muzviitiko zvehupenyu, uye anowanzoshandiswa mukuongorora kwekushanda, kutsvagisa antibody, kuvandudza zvinodhaka uye mamwe minda.Nekuvandudzwa kwebiotechnology uye peptide synthesis tekinoroji, mishonga yakawanda yepeptide yakagadzirwa uye inoshandiswa mukiriniki.
Pane zvakawanda zvakasiyana-siyana zvekugadzirisa peptide, izvo zvinogona kungokamurwa kuva post modification uye process modification (uchishandisa yakatorwa amino acid modification), uye N-terminal modification, C-terminal modification, side chain modification, amino acid modification, skeleton modification, nezvimwewo, zvichienderana nenzvimbo yekushandura (Mufananidzo 1).Senzira yakakosha yekushandura iyo huru cheni chimiro kana mativi emaketani mapoka emaketani epeptide, peptide gadziriso inogona kunyatso shandura iyo yemuviri uye makemikari zvimiro zvepeptide makomponi, kuwedzera kunyungudika kwemvura, kurebesa nguva yekuita mu vivo, kushandura kugovera kwavo biological, kubvisa immunogenicity. , kuderedza chepfu mhedzisiro, nezvimwewo. Mubepa rino, akati wandei makuru ekugadzirisa peptide maitiro uye maitiro awo anounzwa.
1. Kufambisa bhasikoro
Cyclic peptides ane akawanda maapplication mubiomedicine, uye akawanda echisikigo peptides ane biological chiitiko ari cyclic peptides.Nekuti ma cyclic peptides anowanzo kuve akaomarara kupfuura mutsara peptides, iwo akanyanya kurwisa kune digestive system, anogona kurarama mudumbu rekugaya, uye anoratidza hukama hwakasimba kune zvakanangwa zvinogamuchirwa.Cyclization ndiyo nzira yakatwasuka yekugadzira cyclic peptides, kunyanya kune peptides ine hombe skeleton.Zvinoenderana neiyo cyclization modhi, inogona kukamurwa kuita padivi ketani-parutivi cheni mhando, terminal - yedivi ketani mhando, terminal - terminal mhando (kumagumo kusvika kumagumo mhando).
(1) sidechain-to-sidechain
Rudzi rwakajairika rwepadivi-cheni kuenda kudivi-cheni cyclization ndeye disulfide bridging pakati pemasara ecysteine.Iyi cyclization inounzwa nembiri ye cysteine residues ichidzivirirwa uyezve oxidized kuita disulfide zvisungo.Polycyclic synthesis inogona kuwanikwa nekusarudza kubviswa kwe sulfhydryl mapoka ekudzivirira.Cyclization inogona kuitwa mune post-dissociation solvent kana pane pre-dissociation resin.Cyclization paresin inogona kusashanda pane solvent cyclization nekuti mapeptides ari paresin haagadzirike kuumba cyclified conformations.Imwe mhando yedivi-cheni - padivi ketani cyclization kuumbwa kwechimiro cheamide pakati peaspartic acid kana glutamic acid yakasara uye base amino acid, izvo zvinoda kuti boka rekudzivirira cheni yedivi rikwanise kubviswa zvakasarudzika kubva papolypeptide. pane resin kana mushure mekuparadzaniswa.Mhando yechitatu yeside-chain - side chain cyclization ndiko kuumbwa kwe diphenyl ethers ne tyrosine kana p-hydroxyphenylglycine.Iri rudzi rwekutenderera muzvigadzirwa zvechisikigo rinongowanikwa muzvigadzirwa zvehutachiona, uye zvigadzirwa zvecyclization zvinowanzova nemishonga inogona kuve yakakosha.Kugadzirira kwemakomponi aya kunoda yakasarudzika mamiriro ekuita, saka haawanzo shandiswa mukubatanidzwa kweakajairwa peptides.
(2) terminal-to-sidechain
Terminal-side chain cyclization inowanzobatanidza C-terminal neboka reamino re lysine kana ornithine side chain, kana N-terminal ine aspartic acid kana glutamic acid side chain.Imwe polypeptide cyclization inogadzirwa nekugadzira ether zvisungo pakati peterminal C uye serine kana threonine padivi cheni.
(3) Terminal kana musoro-to-muswe mhando
Chain polypeptides inogona kutenderedzwa musolvent kana kugadzikwa pane resin nedivi cheni cyclation.Kudzika kwakadzika kwepeptides kunofanirwa kushandiswa musolvent centralization kudzivirira oligomerization yepeptides.Goho remusoro-kune-muswe synthetic ring polypeptide zvinoenderana nekutevedzana kweketani polypeptide.Naizvozvo, usati wagadzirira cyclic peptides pamwero mukuru, raibhurari yeinobvira yakasungwa lead peptides inofanira kutanga yagadzirwa, ichiteverwa necyclization kuti uwane kutevedzana nemhedzisiro yakanaka.
2. N-methylation
N-methylation pakutanga inoitika mumapeptide echisikigo uye inounzwa mune peptide synthesis kudzivirira kuumbwa kwehydrogen zvisungo, nekudaro zvichiita kuti peptides irambe ichipikisa biodegradation uye kubvumidzwa.Synthesis ye peptides uchishandisa N-methylated amino acid derivatives ndiyo inonyanya kukosha nzira.Pamusoro pezvo, Mitsunobu reaction yeN-(2-nitrobenzene sulfonyl chloride) polypeptide-resin intermediates ine methanol inogonawo kushandiswa.Iyi nzira yakashandiswa kugadzira cyclic peptide maraibhurari ane N-methylated amino acids.
3. Phosphorylation
Phosphorylation ndeimwe yeakajairika post-shanduro shanduko mune zvakasikwa.Mumasero emunhu, anopfuura makumi matatu muzana emapuroteni ane phosphorylated.Phosphorylation, kunyanya inodzoreredzwa phosphorylation, inoita basa rakakosha mukudzora akawanda cellular maitiro, senge chiratidzo chekufambisa, gene expression, cell cycle uye cytoskeleton regulation, uye apoptosis.
Phosphorylation inogona kucherechedzwa pamhando dzakasiyana dzeamino acid zvisaririra, asi zvinonyanya kuzivikanwa phosphorylation zvinongedzo serine, threonine, uye tyrosine zvisaririra.Phosphotyrosine, phosphothreonine, uye phosphoserine derivatives inogona kuunzwa mumapeptides panguva yekubatanidza kana kuumbwa mushure mepeptide synthesis.Kusarudza phosphorylation inogona kuwanikwa uchishandisa zvakasara zveserine, threonine, uye tyrosine izvo zvinosarudza kubvisa mapoka ekudzivirira.Mamwe maphosphorylation reagents anogona zvakare kuunza phosphoric acid mapoka mu polypeptide nekugadziriswa kwepositi.Mumakore achangopfuura, saiti-specific phosphorylation ye lysine yakagadziriswa uchishandisa kemikari inosarudza Staudinger-phosphite reaction (Mufananidzo 3).
4. Myristoylation uye palmitoylation
Acylation yeN-terminal ine fatty acids inobvumira peptides kana mapuroteni kuti asunge kune cell membranes.Iyo myridamoylated sequence paN-terminal inogonesa Src mhuri protein kinases uye reverse transcriptase Gaq mapuroteni kuti atariswe kusunga kune cell membranes.Myristic acid yakabatanidzwa neN-terminal ye resin-polypeptide ichishandisa yakajairwa coupling maitiro, uye mhedzisiro lipopeptide inogona kuparadzaniswa pasi pemamiriro akajairwa uye kucheneswa neRP-HPLC.
5. Glycosylation
Glycopeptides yakadai sevancomycin uye teicolanin mishonga inorwisa mabhakitiriya inokosha pakurapa utachiona husingaurayiwi nemishonga, uye mamwe glycopeptides anowanzoshandiswa kukurudzira immune system.Pamusoro pezvo, sezvo akawanda maantigens ehutachiona ari glycosylated, zvine kukosha kukuru kudzidza glycopeptides yekuvandudza kurapa kwehutachiona.Kune rimwe divi, zvakaonekwa kuti mapuroteni ari pasero membrane ye tumor cell anoratidza abnormal glycosylation, izvo zvinoita kuti glycopeptides iite basa rakakosha mugomarara uye bundu immune immune immune research.Glycopeptides inogadzirwa neFmoc/t-Bu nzira.Glycosylated residues, senge threonine uye serine, inowanzounzwa mumapolypeptides nepentafluorophenol ester activated fMOCs kuchengetedza glycosylated amino acids.
6. Isoprene
Isopentadienylation inoitika pane cysteine residues mudivi ketani pedyo neC-terminal.Protein isoprene inogona kuvandudza sero membrane affinity uye kugadzira protein-protein kupindirana.Isopentadienate mapuroteni anosanganisira tyrosine phosphatase, diki GTase, cochaperone mamorekuru, nuclear lamina, uye centromeric kusunga mapuroteni.Isoprene polypeptides inogona kugadzirwa uchishandisa isoprene pane resins kana nekuunza cysteine derivatives.
7. Polyethylene glycol (PEG) kugadziriswa
PEG shanduko inogona kushandiswa kuvandudza protein hydrolytic kugadzikana, biodistribution uye peptide solubility.Kuunzwa kwemaketani ePEG kumapeptide kunogona kuvandudza zvimiro zvavo zvemishonga uye zvakare kurambidza iyo hydrolysis yepeptides neproteolytic enzymes.PEG peptides inopfuura nepakati peglomerular capillary cross chikamu zviri nyore kupfuura peptides akajairwa, zvichideredza zvakanyanya kubvumidzwa kwetsvo.Nekuda kwekuwedzera kushanda kwehafu yehupenyu hwePEG peptides mu vivo, iyo yakajairika kurapwa mwero inogona kuchengetedzwa neakaderera madosi uye isingawanzo dhiri peptide mishonga.Nekudaro, PEG shanduko inewo yakaipa mhedzisiro.Huwandu hukuru hwePEG hunodzivirira iyo enzyme kubva mukusvibisa peptide uye zvakare inoderedza kusungirirwa kwepeptide kune inotarirwa receptor.Asi kushamwaridzana kwakaderera kwePEG peptides kunowanzo kuderedzwa nekurebesa kwavo pharmacokinetic hafu yeupenyu, uye nekuvepo mumuviri kwenguva refu, PEG peptides ine mukana wakakura wekunyudzwa mumatishu anonangwa.Naizvozvo, PEG polymer zvirevo zvinofanirwa kugadziridzwa kuitira mhedzisiro yakakwana.Kune rimwe divi, PEG peptides inoungana muchiropa nekuda kwekuderedzwa kwerenal clearance, zvichikonzera macromolecular syndrome.Naizvozvo, gadziridzo dzePEG dzinoda kugadzirwa zvakanyanya kana peptides ichishandiswa kuongororwa kwezvinodhaka.
Mapoka akajairika ekugadzirisa PEG modifiers anogona kupfupikiswa sezvizvi: 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 (yakadai sepropional-ald, butyrALD), acrylic base (-acrylate-acrl), azido-azide, biotinyl - Biotin, Fluorescein, glutaryl -GA, Acrylate Hydrazide, alkyne-alkyne, p-toluenesulfonate -OTs, succinimide succinate -SS, etc. PEG derivatives ne carboxylic acids inogona kubatanidzwa kune n-terminal amines kana lysine side chain.Amino-activated PEG inogona kubatanidzwa kune aspartic acid kana glutamic acid parutivi maketani.Mal-activated PEG inogona kubatanidzwa kune mercaptan yeakadzivirirwa zvizere cysteine side maketani [11].PEG modhifita dzinowanzoiswa sezvizvi (chinyorwa: mPEG is methoxy-PEG, CH3O-(CH2CH2O)n-CH2CH2-OH) :
(1) yakatwasuka ketani PEG modifier
mPEG-SC, mPEG-SCM, mPEG-SPA, mPEG-OTs, mPEG-SH, mPEG-ALD, mPEG-butyrALD, mPEG-SS
(2) bifunctional PEG modifier
HCOO-PEG-COOH, NH2-PEG-NH2, OH-PEG-COOH, OH-PEG-NH2, HCl·NH2-PEG-COOH, MAL-PEG-NHS
(3) branching PEG modifier
(mPEG)2-NHS, (mPEG)2-ALD, (mPEG)2-NH2, (mPEG)2-MAL
8. Biotinization
Biotin inogona kusungwa zvakasimba neavidin kana streptavidin, uye simba rekubatanidza rinotove pedyo necovalent bond.Biotin-yakanyorwa peptides inowanzoshandiswa mu immunoassay, histocytochemistry, uye fluorescence-based flow cytometry.Akanyorwa maantibiotin antibodies anogona kushandiswawo kusunga biotinylated peptides.Zvinyorwa zveBiotin zvinowanzobatanidzwa kune lysine side chain kana N terminal.6-aminocaproic acid inowanzoshandiswa sechisungo pakati pepeptides uye biotin.Iyo bhondi inoshanduka mukusunga kune substrate uye inosunga zviri nani pamberi pekudzivisa steric.
9. Fluorescent labeling
Fluorescent labeling inogona kushandiswa kutsvaga polypeptides mumasero mapenyu uye kudzidza ma enzymes uye maitiro ekuita.Tryptophan (Trp) is fluorescent, saka inogona kushandiswa kune intrinsic labeling.Iyo emission spectrum ye tryptophan inoenderana nenharaunda yenharaunda uye inodzikira nekuderera kwe solvent polarity, chivakwa chinobatsira pakuona peptide chimiro uye receptor kusunga.Tryptophan fluorescence inogona kudzimwa neprotonated aspartic acid uye glutamic acid, inogona kuderedza kushandiswa kwayo.Dansyl chloride group (Dansyl) ine fluorescent yakanyanya kana yakasungwa kuboka remamino uye inowanzoshandiswa se fluorescent label yeamino acids kana mapuroteni.
Fluorescence resonance Energy kutendeuka (FRET) inobatsira kune zvidzidzo zve enzyme.Kana FRET ikaiswa, iyo substrate polypeptide inowanzo ine fluorescence-labeling boka uye fluorescence-quenching boka.Mapoka akanyorwa efluorescent anodzimwa neanodzima kuburikidza neasina-photon simba rekufambisa.Kana iyo peptide ikaparadzaniswa kubva kune enzyme iri mubvunzo, boka rekunyora rinoburitsa fluorescence.
10. Cage polypeptides
Cage peptides ane optically anobvisika ekudzivirira mapoka anodzivirira iyo peptide kubva pakusunga kune receptor.Kana yakafumurwa kune UV mwaranzi, iyo peptide inobatidzwa, ichidzoreredza hukama hwayo kune receptor.Nekuti iyi yekuona activation inogona kudzorwa zvichienderana nenguva, amplitude, kana nzvimbo, cage peptides inogona kushandiswa kudzidza maitiro anoitika mumaseru.Mapoka ekudzivirira anonyanya kushandiswa ekeji polypeptides ndiwo 2-nitrobenzyl mapoka uye zvinobva zvawo, izvo zvinogona kuunzwa mu peptide synthesis kuburikidza nekudzivirira amino acid kubva.Amino acid kubva kune akagadzirwa lysine, cysteine, serine, uye tyrosine.Aspartate uye glutamate derivatives, zvisinei, hazviwanzo kushandiswa nekuda kwekunzwa kwavo kubhasikoro panguva yepeptide synthesis uye dissociation.
11. Polyantigenic peptide (MAP)
Mapfupi peptides kazhinji haana kudzivirirwa uye anofanirwa kubatanidzwa kune anotakura mapuroteni kuti abudise masoja ekudzivirira chirwere.Polyantigenic peptide (MAP) inoumbwa nemapeptide akawanda akafanana akabatana nelysine nuclei, iyo inogona kunyatso ratidza yakakwirira potency immunogens uye inogona kushandiswa kugadzirira peptide-inotakura mapuroteni couplets.MAP polypeptides inogona kugadzirwa neyakasimba chikamu synthesis paMAP resin.Nekudaro, kubatanidza kusakwana kunoguma nekushaikwa kana kuderedzwa peptide cheni pane mamwe mapazi uye nekudaro hairatidze zvimiro zvepakutanga MAP polypeptide.Seimwe nzira, peptides inogona kugadzirirwa nekucheneswa zvakasiyana uye yozobatanidzwa kuMAP.Iyo peptide inoteedzana yakasungirirwa kune peptide musimboti yakanyatsotsanangurwa uye nyore kuratidzwa nehukuru spectrometry.
Mhedziso
Peptide shanduko inzira yakakosha yekugadzira peptides.Kemikari yakagadziridzwa peptides haingogone kuchengetedza yakakwira biological chiitiko, asiwo zvinobudirira kudzivirira zvipingamupinyi zve immunogenicity uye chepfu.Panguva imwecheteyo, shanduko yemakemikari inogona kupa peptides nezvimwe zvitsva zvakanakisa zvivakwa.Mumakore achangopfuura, nzira yeC activation ye-post-modification ye polypeptides yakakurumidza kugadzirwa, uye zvakawanda zvakakosha zvakawanikwa.
Nguva yekutumira: Mar-20-2023