Peptides bụ klaasị ogige etolite site na njikọ nke ọtụtụ amino acid site na njikọ peptide.Ha dị ebe niile na ihe ndị dị ndụ.Ruo ugbu a, a chọtala iri puku kwuru iri puku peptides n'ime ihe ndị dị ndụ.Peptides na-arụ ọrụ dị mkpa n'ịhazi ọrụ arụ ọrụ nke usoro dị iche iche, akụkụ ahụ, anụ ahụ na sel na ọrụ ndụ, a na-ejikarị ya eme ihe na nyocha ọrụ, nchọpụta mgbochi, mmepe ọgwụ na mpaghara ndị ọzọ.Site na mmepe nke teknụzụ biotechnology na teknụzụ njikọ peptide, a na-emepụta ọtụtụ ọgwụ peptide ma tinye ya n'ụlọ ọgwụ.
Enwere mgbanwe dị iche iche nke peptide dị iche iche, nke enwere ike kewaa n'ime mgbanwe post na mgbanwe usoro (iji amino acid emepụtara), na N-terminal mgbanwe, mgbanwe C-terminal, mgbanwe n'akụkụ, mgbanwe amino acid, mgbanwe ọkpụkpụ, wdg, dabere na saịtị mgbanwe (Fig 1).Dị ka ụzọ dị mkpa iji gbanwee isi ihe owuwu ma ọ bụ n'akụkụ yinye nke agbụ peptide, mgbanwe peptide nwere ike ịgbanwe nke ọma nke anụ ahụ na kemịkal nke ogige peptide, na-abawanye solubility mmiri, ogologo oge na-eme ihe na vivo, gbanwee nkesa ndu ha, wepụ immunogenicity. , belata mmetụta ndị na-egbu egbu, wdg. N'akwụkwọ a, a na-ewebata ọtụtụ atụmatụ mgbanwe peptide dị mkpa na njirimara ha.
1. Ịgba ígwè
Cyclic peptides nwere ọtụtụ ngwa na biomedicine, na ọtụtụ peptides eke nwere ọrụ ndu bụ peptides cyclic.N'ihi na peptides cyclic na-esikarị ike karịa peptides linear, ha na-eguzogide ọgwụ na usoro nri nri, nwere ike ịdị ndụ na tract digestive, ma gosipụta mmekọrịta siri ike maka ndị na-anabata ihe.Cyclization bụ ụzọ kacha zie ezie iji mepụta peptides cyclic, ọkachasị maka peptides nwere nnukwu ọkpụkpụ arụrụ arụ.Dị ka usoro cyclization si dị, enwere ike kewaa ya n'ime ụdị agbụ-n'akụkụ, njedebe - ụdị n'akụkụ, njedebe - ụdị njedebe (njedebe na njedebe).
(1) sidechain-to-sidechain
Ụdị ịgbagharị n'akụkụ agbụ ruo n'akụkụ a na-ahụkarị bụ ijikọ disulfide n'etiti ihe fọdụrụ na cysteine.A na-ewebata cyclization a site na ụzọ abụọ nke ihe fọdụrụ na cysteine na-emebi emebi wee mechaa oxidized iji mepụta njikọ disulfide.Enwere ike nweta njikọ polycyclic site n'iwepụ otu nchebe sulfhydryl.Enwere ike ime cyclization ma ọ bụ n'ime ihe mgbaze mgbe nkesa gasịrị ma ọ bụ na resin tupu nkewa.Cyclization na resins nwere ike ịdị irè karịa ịgbagharị mgbaze n'ihi na peptides na resins anaghị etolite ngwa ngwa cyclified conformations.Ụdị ọzọ nke n'akụkụ - cyclization yinye n'akụkụ bụ nhazi nke amide n'etiti aspartic acid ma ọ bụ glutamic acid residue na amino acid ntọala, nke na-achọ ka a ga-enwe ike iwepụ otu nchebe n'akụkụ site na polypeptide. na resin ma ọ bụ mgbe dissociation.Ụdị nke atọ nke n'akụkụ - cyclization yinye n'akụkụ bụ nhazi nke diphenyl ethers site na tyrosine ma ọ bụ p-hydroxyphenylglycine.Ụdị ịgba ígwè a na ngwaahịa ndị sitere n'okike bụ nanị na ngwaahịa microbial, na ngwaahịa cyclization na-enwekarị uru ọgwụ.Nkwadebe nke ogige ndị a chọrọ ọnọdụ mmeghachi omume pụrụ iche, n'ihi ya, a naghị ejikarị ha eme ihe na njikọ nke peptides.
(2) ọnụ-na-sidechain
Ịgbagharị yinye n'akụkụ njedebe na-agụnyekarị C-terminal na otu amino group nke lysine ma ọ bụ ornithine n'akụkụ, ma ọ bụ N-terminal nwere aspartic acid ma ọ bụ glutamic acid n'akụkụ.A na-eme cyclization polypeptide ndị ọzọ site n'ịme njikọ ether n'etiti eriri C na serine ma ọ bụ threonine n'akụkụ.
(3) Ụdị njedebe ma ọ bụ isi-na-ọdụ
Enwere ike ịgbanye polypeptides yinye okirikiri n'ime ihe mgbaze ma ọ bụ dokwa ya na resin n'akụkụ ịgbagharị yinye n'akụkụ.Ekwesịrị iji obere mkpokọta peptides mee ihe na nhazi ihe mgbaze iji zere oligomerization nke peptides.Mkpụrụ nke mgbanaka sịntetik polypeptide isi na ọdụ dabere na usoro nke yinye polypeptide.Ya mere, tupu ịkwadebe cyclic peptides n'ọtụtụ buru ibu, a ga-ebu ụzọ mepụta ọbá akwụkwọ nke peptides lead nwere ike ibu ụzọ mepụta, na-esote cyclization iji chọta usoro nke nwere nsonaazụ kacha mma.
2. N-methylation
N-methylation na-amalite na peptides eke ma weba ya n'ime njikọ peptide iji gbochie nguzobe nke njikọ hydrogen, si otú ahụ na-eme ka peptides na-eguzogide ọgwụ na biodegradation na mkpochapụ.Njikọ nke peptides na-eji N-methylated amino acid Nwepụta bụ ụzọ kachasị mkpa.Na mgbakwunye, a pụkwara iji mmeghachi omume Mitsunobu nke N- (2-nitrobenzene sulfonyl chloride) polypeptide-resin intermediates na methanol.Ejila usoro a iji kwado ọba akwụkwọ peptide cyclic nwere amino acid N-methylated.
3. Phosphorylation
Phosphorylation bụ otu n'ime mgbanwe mgbanwe ntụgharị asụsụ a na-ahụkarị na okike.N'ime sel mmadụ, ihe karịrị 30% nke protein bụ phosphorylate.Phosphorylation, karịsịa phosphorylation reversible, na-arụ ọrụ dị mkpa n'ịchịkwa ọtụtụ usoro cellular, dị ka ntụgharị mgbaàmà, okwu mkpụrụ ndụ ihe nketa, usoro cell na ụkpụrụ cytoskeleton, na apoptosis.
Enwere ike ịhụ phosphorylation n'ụdị amino acid dị iche iche, mana ebumnuche phosphorylation a na-ahụkarị bụ serine, threonine na tyrosine.Enwere ike iwebata phosphotyrosine, phosphothreonine na phosphoserine n'ime peptides n'oge njikọ ma ọ bụ guzobe mgbe njikọ peptide gasịrị.Enwere ike nweta phosphorylation ahọpụtara site na iji mfu nke serine, threonine, na tyrosine na-ahọrọ nke na-ewepụ otu nchebe.Ụfọdụ reagents phosphorylation nwekwara ike iwebata otu phosphoric acid n'ime polypeptide site na mgbanwe mgbanwe.N'ime afọ ndị na-adịbeghị anya, a na-enweta phosphorylation saịtị nke lysine site na iji mmeghachi omume Staudinger-phosphite na-ahọrọ (Njirimara 3).
4. Myristoylation na palmitoylation
Acylation nke N-terminal nwere fatty acids na-enye ohere ka peptides ma ọ bụ protein kekọta na membranes cell.Usoro myridamoylated na N-terminal na-enyere Src protein protein kinases na tụgharịa transcriptase protein Gaq ka edoro anya iji jikọta na membranes cell.Ejikọtara myristic acid na N-terminal nke resin-polypeptide site na iji mmeghachi omume njikọta ọkọlọtọ, na nsonaazụ lipopeptide nwere ike kewaa n'okpuru ọnọdụ ọkọlọtọ ma sachaa ya site na RP-HPLC.
5. Glycosylation
Glycopeptides dị ka vancomycin na teicolanin bụ ọgwụ nje dị mkpa maka ọgwụgwọ ọrịa nje na-eguzogide ọgwụ, a na-ejikarị glycopeptides ndị ọzọ na-akpali usoro ahụ ji alụso ọrịa ọgụ.Na mgbakwunye, ebe ọ bụ na ọtụtụ microbial antigens bụ glycosylated, ọ dị oke mkpa ịmụ glycopeptides maka ịkwalite mmetụta ọgwụgwọ ọrịa.N'aka nke ọzọ, a chọpụtala na protein ndị dị na cell membrane nke mkpụrụ ndụ tumor na-egosipụta glycosylation na-adịghị mma, nke na-eme ka glycopeptides na-arụ ọrụ dị mkpa na ọrịa cancer na ọrịa cancer na-eme nchọpụta.A na-akwado Glycopeptides site na usoro Fmoc/t-Bu.A na-ebutekarị ihe fọdụrụ glycosylated, dị ka threonine na serine n'ime polypeptides site na pentafluorophenol ester na-arụ ọrụ fMOCs iji chebe amino acid glycosylated.
6. Isoprene
Isopentadienylation na-apụta na ihe fọdụrụ na cysteine n'agbụ akụkụ dị nso C-terminal.Protein isoprene nwere ike imezi mmekọrịta nke akpụkpọ ahụ cell ma mepụta mmekọrịta protein-protein.Ndị na-edozi ahụ nke a na-ekewaghị ekewa gụnyere tyrosine phosphatase, obere GTase, ụmụ irighiri ihe cochaperone, lamina nuklia, na protein na-ejikọta centromeric.Enwere ike ịkwadebe isoprene polypeptides site na iji isoprene na resins ma ọ bụ site na iwebata ihe mmepụta cysteine.
7. Polyethylene glycol (PEG) mgbanwe
Enwere ike iji mgbanwe PEG kwalite nkwụsi ike protein hydrolytic, nkesa biodistribution na peptide solubility.Iwebata agbụ PEG na peptides nwere ike melite akụrụngwa ọgwụ ha yana gbochie hydrolysis nke peptides site na enzymes proteolytic.PEG peptides na-agafe na ngalaba glomerular capillary cross n'ụzọ dị mfe karịa peptides nkịtị, na-ebelata nkwụsị nke akụrụ.N'ihi ogologo ndụ ọkara ndụ PEG peptides na vivo na-arụ ọrụ, enwere ike idowe ọkwa ọgwụgwọ nkịtị site na obere doses yana ọgwụ peptide na-adịkarị obere.Agbanyeghị, mgbanwe PEG nwekwara mmetụta ọjọọ.Nnukwu PEG na-egbochi enzyme ahụ ka ọ ghara imebi peptide ma belata njikọ nke peptide na onye na-anabata ya.Ma PEG peptides 'dị ala mmekọrịta na-emekarị ka ọ kwụsị site na ọkara ndụ ọgwụ pharmacokinetic ha dị ogologo, na site na ịnọ n'ime ahụ ogologo oge, peptides PEG nwere ohere dị ukwuu nke ịbanye n'ime anụ ahụ lekwasịrị anya.Ya mere, ekwesịrị ịhazi nkọwapụta PEG polymer maka nsonaazụ kacha mma.N'aka nke ọzọ, peptides PEG na-agbakọta n'ime imeju n'ihi mbelata mkpochapụ nke akụrụ, na-ebute ọrịa macromolecular.Ya mere, mgbanwe PEG kwesịrị ka e jiri nlezianya mee nke ọma mgbe a na-eji peptides eme nyocha ọgwụ.
Enwere ike ichikota otu mgbanwe mgbanwe nke PEG modifiers dị ka ndị a: Amino (-amine) -NH2, aminomethyl-Ch2-NH2, hydroxy-OH, carboxy-Cooh, sulfhydryl (-Thiol) -SH, Maleimide -MAL, carbonate succinimide - SC, succinimide acetate -SCM, succinimide propionate -SPA, n-hydroxysuccinimide -NHS, Acrylate-ch2ch2cooh, aldehyde -CHO (dị ka propional-ald, butyrALD), acrylic base (-acrylate-acrl), azido-azide, biotinyl - Biotin, Fluorescein, glutaryl -GA, Acrylate Hydrazide, alkyne-alkyne, p-toluenesulfonate -OTs, succinimide succinate -SS, wdg. PEG mmepụta na carboxylic acid nwere ike jikọtara na n-terminal amines ma ọ bụ lysine n'akụkụ agbụ.PEG na-arụ ọrụ Amino nwere ike jikọta ya na aspartic acid ma ọ bụ ụdọ akụkụ glutamic acid.Enwere ike ijikọ PEG na-adịghị arụ ọrụ na mercaptan nke agbụ akụkụ cysteine emebere nke ọma [11].A na-ekekarị ndị mgbanwe PEG dị ka ndị a (mara: mPEG bụ methoxy-PEG, CH3O-(CH2CH2O) n-CH2CH2-OH):
(1) ogologo yinye PEG modifier
mPEG-SC, mPEG-SCM, mPEG-SPA, mPEG-OTs, mPEG-SH, mPEG-ALD, mPEG-butyrALD, mPEG-SS
(2) Mgbanwe PEG bifunctional
HCOO-PEG-COOH, NH2-PEG-NH2, OH-PEG-COOH, OH-PEG-NH2, HCl·NH2-PEG-COOH, MAL-PEG-NHS
(3) Mgbanwe PEG nke alaka
(mPEG) 2-NHS, (mPEG) 2-ALD, (mPEG) 2-NH2, (mPEG) 2-MAL
8. Biotinization
Enwere ike ijikọ biotin na avidin ma ọ bụ streptavidin, na ike njide dị nso na njikọ nke covalent.A na-ejikarị peptides akara biotin mee ihe na immunoassay, histocytochemistry, na cytometry na-asọpụta nke fluorescence.A nwekwara ike iji ọgwụ mgbochi antibiotin akpọnyere aha iji kechie peptides biotinylated.A na-ejikọkarị akara biotin na agbụ akụkụ lysine ma ọ bụ ọdụ N.A na-ejikarị 6-aminocaproic acid mee ihe dị ka njikọ n'etiti peptides na biotin.Njikọ ahụ na-agbanwe agbanwe na ijikọ na mkpụrụ osisi ma na-ejikọta nke ọma na ọnụnọ nke mgbochi siri ike.
9. Ntube nke fluorescent
Enwere ike iji akara fluorescent iji chọpụta polypeptides na sel dị ndụ yana mụọ enzymes na usoro ọrụ.Tryptophan (Trp) bụ fluorescent, yabụ enwere ike iji ya mee akara n'ime ime.Ụdị dị iche iche nke tryptophan na-adabere na gburugburu gburugburu ma na-ebelata site na mbelata ihe mgbaze polarity, ihe onwunwe bara uru maka ịchọpụta nhazi peptide na njide nnabata.Enwere ike imenyụ fluorescence tryptophan site na protonated aspartic acid na glutamic acid, nke nwere ike belata ojiji ya.Otu Dansyl chloride (Dansyl) na-enwe nnukwu fluorescent mgbe ejikọtara ya na otu amino ma na-ejikarị ya dị ka akara fluorescent maka amino acid ma ọ bụ protein.
Fluorescence resonance Energy mgbanwe (FRET) bara uru maka ọmụmụ enzyme.Mgbe etinyere FRET, mkpụrụ osisi polypeptide na-enwekarị otu akara akara fluorescence na otu na-emenyụ ọkụ.Ndị na-emenyụ ọkụ na-emenyụ otu ndị akpọrọ fluorescent site na mbufe ike na-abụghị foto.Mgbe peptide kewapụrụ na enzyme a na-ajụ ajụjụ, otu akara akara na-ewepụta fluorescence.
10. Cage polypeptides
Cage peptides nwere otu nchebe nke mbughari anya nke na-echebe peptide site na ijikọ na onye na-anabata ya.Mgbe ekpughere ya na radieshon UV, peptide na-arụ ọrụ, na-eweghachi mmekọrịta ya na onye na-anabata ya.N'ihi na enwere ike ịchịkwa ngwa ngwa ngwa a dabere na oge, njupụta, ma ọ bụ ọnọdụ, enwere ike iji peptides cage mụọ mmeghachi omume na-eme na sel.Otu nchebe a na-ejikarị eme ihe maka polypeptides ọnụ bụ 2-nitrobenzyl otu na usoro ha, nke enwere ike iwebata na peptide synthesis site na nchebe amino acid.Amino acid emepụtara bụ lysine, cysteine, serine, na tyrosine.Otú ọ dị, a naghị ejikarị aspartate na glutamate eme ihe n'ihi ike ha nwere na cyclization n'oge njikọ peptide na dissociation.
11. Polyantigenic peptide (MAP)
Peptides dị mkpụmkpụ anaghị alụso ọrịa ọgụ, a ga-ejikọrịrị ya na protein ndị na-ebu ibu iji mepụta ọgwụ mgbochi.Polyantigenic peptide (MAP) bụ nke nwere ọtụtụ peptides yiri ya jikọtara ya na lysine nuclei, nke nwere ike ịkọwapụta immunogens dị elu nke ọma ma nwee ike iji dozie njikọ protein peptide-ebu.Enwere ike ịhazi MAP polypeptides site na njikọ siri ike na resin MAP.Agbanyeghị, njikọta ezughị ezu na-ebute ụdọ peptide na-efu efu ma ọ bụ gbajie n'ụfọdụ alaka wee si otú a egosipụtaghị njirimara nke mbụ MAP polypeptide.Dị ka ihe ọzọ, peptides nwere ike ịkwadebe ma sachaa iche iche wee jikọta ya na MAP.Usoro peptide jikọtara na peptide core bụ nke akọwapụtara nke ọma na nke dị mfe site na nnukwu spectrometry.
Mmechi
Mgbanwe peptide bụ ụzọ dị mkpa e si emepụta peptides.peptides gbanwere kemịkalụ nwere ike ọ bụghị naanị ịnọgide na-arụ ọrụ ndu dị elu, kamakwa na-ezere ihe ndọghachi azụ nke immunogenicity na nsi.N'otu oge ahụ, mgbanwe kemịkalụ nwere ike inye peptides nwere ụfọdụ ọmarịcha ihe ọhụrụ.N'ime afọ ndị na-adịbeghị anya, usoro nke CH na-arụ ọrụ maka mgbanwe mgbanwe nke polypeptides ka emepụtara ngwa ngwa, na ọtụtụ ihe dị mkpa enwetawo.
Oge nzipu: Mar-20-2023