Peptides waa nooc ka mid ah xeryahooda ay sameeyeen isku xirka amino acids badan iyada oo loo marayo bonds peptide.Waxay meel walba kaga jiraan noolaha noolaha.Ilaa hadda, tobanaan kun oo peptides ayaa laga helay noolaha.Peptides-ku waxay door muhiim ah ka ciyaaraan nidaaminta hawlaha shaqada ee hababka kala duwan, xubnaha, unugyada iyo unugyada iyo hawlaha nolosha, waxaana badanaa loo isticmaalaa falanqaynta shaqada, cilmi-baarista antibody, horumarinta daroogada iyo qaybaha kale.Horumarinta tignoolajiyada bayotechnoolajiyada iyo tignoolajiyada isku dhafka peptide, dawooyin badan oo peptide ah ayaa la sameeyay oo lagu dabaqay rugta caafimaadka.
Waxaa jira noocyo kala duwan oo wax ka beddelka peptide, kaas oo si fudud loo qaybin karo wax ka beddelka boostada iyo habraaca wax ka beddelka (iyadoo la adeegsanayo beddelka amino acid ee la soo saaray), iyo beddelka N-terminal, beddelka C-terminal, beddelka silsiladda dhinaca, beddelka amino acid beddelka, beddelka qalfoofka, iwm, iyada oo ku xidhan goobta wax ka beddelka (Jaantuska 1).Sida macne muhiim ah oo lagu beddelo qaabdhismeedka silsiladda ugu weyn ama kooxaha silsiladaha dhinaca silsiladaha peptide, wax ka beddelka peptide wuxuu si wax ku ool ah u beddeli karaa sifooyinka jirka iyo kiimikaad ee xeryahooda peptide, kordhinta milanka biyaha, kordhiyaan waqtiga ficilka ee vivo, beddelaan qaybinta noolaha, baabi'inta difaaca jirka. , yareeya waxyeelada sunta ah, iwm. Warqadan, dhowr xeeladood oo wax ka beddelka peptide-ka ah ayaa la soo bandhigay.
1. Baaskiilada
Cyclic peptides waxay leeyihiin codsiyo badan oo ku saabsan biomedicine, iyo peptides badan oo dabiici ah oo leh dhaqdhaqaaq bayooloji waa peptides wareeg ah.Sababtoo ah peptides cyclic waxay u muuqdaan inay ka adag yihiin peptides-ka tooska ah, waxay si aad ah ugu adkaysanayaan habka dheef-shiidka, waxay ku noolaan karaan habka dheef-shiidka, waxayna muujiyaan xiriir adag oo loogu talagalay soo-dhoweynta bartilmaameedka.Baaskiilaynta ayaa ah habka ugu toosan ee lagu soo saari karo peptides-ka wareegtada ah, gaar ahaan peptides-ka leh qalfoofka qaabdhismeedka wayn.Marka loo eego qaabka baaskiilka, waxaa loo qaybin karaa nooca silsiladda dhinaca silsiladda, terminal - nooca silsiladda dhinaca, terminal - nooca terminal (dhammaadka ilaa dhammaadka).
(1) Silsilad-ilaa-dhinac
Nooca ugu badan ee silsilad-side ilaa silsilad-wareejin waa isku-xidhka disulfide ee u dhexeeya hadhaaga cysteine.Baaskiilayntan waxaa soo bandhigay labo ka mid ah haraaga cysteine-ka oo la ilaalinayo ka dibna oksaydh laga dhigay si loo sameeyo curaarta disulfide.Isku-dubbaridka polycyclic waxaa lagu gaari karaa in si gooni ah looga saaro kooxaha ilaalinta sulfhydryl.Baaskiilaynta waxa lagu samayn karaa dareeraha kala-tagga ka dib ama xabagta kala-tagista ka hor.Baaskiil ku samaynta xabagta waxa laga yaabaa in ay ka waxtar yar tahay baaskiil wadida dareeraha sababta oo ah peptides-ka xabagta ku jira si sahal ah uma sameeyaan is-waafajin wareeg ah.Nooc kale oo ka mid ah silsilad-dhinac-wareejinta silsiladda dhinac ayaa ah samaynta qaab-dhismeedka amide ee u dhexeeya aspartic acid ama glutamic acid hadhaaga iyo amino acid-ka saldhigga, kaas oo u baahan in kooxda ilaalinta silsiladda dhinac ay awoodaan in si door ah looga saaro polypeptide-ka midkoodna. on xabagta ama ka dib marka la kala tago.Nooca saddexaad ee silsilad-dhinac-wareejinta silsiladda dhinac ayaa ah samaynta diphenyl ethers by tyrosine ama p-hydroxyphenylglycine.Baaskiilada noocaan ah ee alaabta dabiiciga ah waxaa laga helaa oo kaliya alaabta microbial-ka ah, iyo alaabada baaskiil wadida inta badan waxay leeyihiin qiimo daawo.Diyaarinta xeryahooda waxay u baahan yihiin xaalado falcelin gaar ah, sidaas darteed inta badan looma isticmaalo isku-darka peptides caadiga ah.
(2) terminal-to-sidechain
Baaskiil-wareejinta silsiladda-dhinaca badiyaa waxay ku lug leedahay C-terminal oo leh kooxda amino ee silsiladda dhinaca lysine ama ornithine, ama N-terminal oo leh aspartic acid ama silsilad dhinaca glutamic acid.Baaskiil kale oo polypeptide ah ayaa lagu sameeyaa iyada oo la samaynayo curaarta ether inta u dhaxaysa terminaalka C iyo serine ama silsiladaha dhinaca threonine.
(3) Terminal ama nooca madax-ilaa-dabada
Silsiladda polypeptides-ka waxaa lagu wadi karaa baaskiilo ama lagu dhejin karaa resin by silsilad wareeg ah.Heerarka hoose ee peptides waa in loo adeegsadaa dhexdhexaadinta dareeraha si looga fogaado oligomerization of peptides.Wax-soo-saarka giraanta synthetic polypeptide madax-ilaa-dabo waxay ku xiran tahay sida ay u kala horreeyaan silsiladda polypeptide-ka.Sidaa darteed, ka hor inta aan la diyaarinin peptides-ka baaskiilka ee cabbirka ballaaran, maktabad ay suurtagal tahay peptides-ka ledhka ee suurtogalka ah waa in marka hore la sameeyaa, oo ay ku xigto baaskiil si loo helo isku xigxiga natiijooyinka ugu fiican.
2. N-methylation
N-methylation asal ahaan waxay ku dhacdaa peptides-ka dabiiciga ah waxaana lagu soo bandhigaa isku-dhafka peptide si looga hortago samaynta curaarta hydrogen, taas oo ka dhigaysa peptides-ka adkaysi u leh biodegradation iyo nadiifinta.Isku-darka peptides-ka iyadoo la adeegsanayo N-methylated amino acid derivatives ayaa ah habka ugu muhiimsan.Intaa waxaa dheer, falcelinta Mitsunobu ee N- (2-nitrobenzene sulfonyl chloride) polypeptide-resin intermediates oo leh methanol sidoo kale waa la isticmaali karaa.Habkan waxa loo isticmaalay in lagu diyaariyo maktabadaha peptide-ka ee meertada leh oo ay ku jiraan N-methylated amino acids.
3. Fosfooraska
Fosforyaalku waa mid ka mid ah isbeddellada ugu caansan ee ka dambeeya turjumaadda dabeecadda.Unugyada aadanaha, in ka badan 30% borotiinada ayaa ku jira fosfooraska.Phosphorylation, gaar ahaan fosforyaalka dib loo rogi karo, ayaa door muhiim ah ka ciyaara xakameynta hababka gacanta ee badan, sida gudbinta calaamadaha, muujinta hidda-wadaha, wareegga unugyada iyo nidaamka cytoskeleton, iyo apoptosis.
Fosforyaalka waxaa lagu arki karaa hadhaaga amino acid kala duwan, laakiin bartilmaameedyada fosforyaalka ugu badan waa serine, threonine, iyo haraaga tyrosine.Fosfotyrosine, phosphothreonine, iyo derivatives phosphoserine ayaa la gelin karaa peptides inta lagu guda jiro synthesization ama la sameeyo ka dib markii peptide synthesis.Fosforyaalka xulashada waxaa lagu gaari karaa iyadoo la isticmaalayo hadhaaga serine, threonine, iyo tyrosine kuwaas oo si door ah meesha uga saaraya kooxaha difaaca.Qaar ka mid ah reageniyeyaasha fosfooraska ayaa sidoo kale soo bandhigi kara kooxaha fosfooraska fosfooraska ee polypeptide ka dib wax ka beddelka.Sannadihii ugu dambeeyay, goobta-fosforyaalka u gaarka ah ee lysine ayaa lagu gaaray iyadoo la isticmaalayo falcelinta Staudinger-phosphite ee kiimikaad ahaan dooratay (Jaantuska 3).
4. Myristoylation iyo palmitoylation
Acylation of the N-terminal oo leh asiidh dufan leh ayaa u oggolaanaysa peptides ama borotiinada inay ku xidhaan xuubka unugyada.Taxanaha myridamoylated ee N-terminal wuxuu awood u siinayaa kinases borotiinka qoyska Src iyo beddelka borotiinada Gaq in la bartilmaameedsado si loogu xidho xuubka unugyada.Myristic acid waxa lagu xidhay N-terminal of resin-polypeptide iyadoo la isticmaalayo falcelinta isku xidhka caadiga ah, iyo natiijada lipopeptide waxaa lagu kala saari karaa xaaladaha caadiga ah waxaana lagu sifeeyaa RP-HPLC.
5. Glycosylation
Glycopeptides sida vancomycin iyo teicolanin ayaa ah antibiyootiga muhiimka ah ee daaweynta caabuqyada bakteeriyada u adkeysata daawada, iyo glycopeptides kale ayaa inta badan loo isticmaalaa kicinta habka difaaca jirka.Intaa waxaa dheer, maadaama antigens badan oo microbial ah ay yihiin glycosylated, waa muhiim in la barto glycopeptides si loo hagaajiyo saameynta daaweynta caabuqa.Dhanka kale, waxaa la ogaaday in borotiinnada ku jira xuubka unugga ee unugyada burooyinka ay muujiyaan glycosylation aan caadi ahayn, taas oo ka dhigaysa glycopeptides inay door muhiim ah ka ciyaaraan kansarka iyo cilmi-baarista difaaca difaaca.Glycopeptides waxaa lagu diyaariyaa habka Fmoc/t-Bu.Hadhaaga Glycosylated, sida threonine iyo serine, ayaa inta badan lagu dhex geliyaa polypeptides by pentafluorophenol ester fMOCs firfircoon si ay u ilaaliyaan glycosylated amino acids.
6. isoprene
Isopentadienylation waxay ku dhacdaa hadhaaga cysteine ee silsiladda dhinaca ee u dhow C-terminal.Protein isoprene waxa uu wanaajin karaa xidhiidhka xuubka unugga oo uu sameeyo isdhexgalka borotiinka-proteinBorotiinnada la go'doomiyay waxaa ka mid ah tyrosine phosphatase, GTase yar, molecules kochaperone, lamina nukliyeer, iyo borotiinada isku xira centromeric.Isoprene polypeptides waxaa lagu diyaarin karaa iyadoo la isticmaalayo isoprene on resins ama iyadoo la soo bandhigayo derivatives cysteine.
7. Wax ka beddelka polyetylen glycol (PEG).
Beddelka PEG waxaa loo isticmaali karaa si loo hagaajiyo xasilloonida borotiinka hydrolytic, qaybinta noole iyo milanka peptide.Soo bandhigida silsiladaha PEG ee peptides waxay wanaajin kartaa sifooyinkooda dawooyinka waxayna sidoo kale joojin karaan hydrolysis ee peptides ee enzymes-ka borotiinka.PEG peptides waxay si ka sahlan u dhex maraan qaybta glomerular capillary capillary si ka sahlan peptides caadiga ah, taas oo aad u yaraynaysa nadiifinta kelyaha.Sababtoo ah nolosha nus-nolosha firfircoon ee PEG peptides in vivo, heerka daawaynta caadiga ah waxaa lagu sii hayn karaa qiyaaso hoose iyo dawooyinka peptide-ka ee soo noqnoqda.Si kastaba ha noqotee, wax ka beddelka PEG wuxuu kaloo leeyahay saameyn xun.Xaddi badan oo PEG ah ayaa ka hortagaya insaymka inuu hoos u dhigo peptide-ka iyo sidoo kale wuxuu yareeyaa ku-xidhka peptide-ka ee soo-dhoweeyaha bartilmaameedka.Laakin xidhiidhka hoose ee PEG peptides waxa caadi ahaan ka baxa noloshooda badhkii farmakookinetic-ka ee dheer, iyo joogitaanka jidhka oo dheer, peptides-ka PEG waxay leeyihiin suurtogalnimo weyn oo ah in lagu nuugo unugyada bartilmaameedka ah.Sidaa darteed, qeexitaannada PEG polymer waa in la hagaajiyaa si loo helo natiijooyin wanaagsan.Dhanka kale, PEG peptides waxay ku ururaan beerka sababtoo ah nadiifinta kelyaha oo yaraatay, taasoo keentay cilladda macromolecular.Sidaa darteed, wax ka beddelka PEG wuxuu u baahan yahay in si taxadar leh loo qaabeeyo marka peptides loo isticmaalo baaritaanka daroogada.
Kooxaha wax ka beddelka guud ee wax-ka-beddelayaasha PEG ayaa qiyaas ahaan loo soo koobi karaa sida soo socota: 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 (sida propional-ald, butyrALD), saldhig acrylic (-acrylate-acrl), azido-azide, biotinyl - Biotin, Fluorescein, glutaryl -GA, Acrylate Hydrazide, alkyne-alkyne, p-toluenesulfonate -OTs, succinimide succinate -SS, iwm.Amino-activated PEG waxa lagu xidhi karaa aspartic acid ama silsiladaha dhinaca glutamic acid.PEG-da aan firfircoonayn waxa lagu xidhi karaa mercaptan ee silsiladaha dhinaca cysteine-ka oo si buuxda u ilaaliya [11].Wax ka beddelayaasha PEG waxaa badanaa loo kala saaraa sida soo socota (xusuusnow: mPEG waa methoxy-PEG, CH3O-(CH2CH2O) n-CH2CH2-OH):
(1) wax ka beddelka silsiladda tooska ah ee PEG
mPEG-SC, mPEG-SCM, mPEG-SPA, mPEG-OTs, mPEG-SH, mPEG-ALD, mPEG-butyrALD, mPEG-SS
(2) Beddeeye PEG oo laba shaqaynaysa
HCOO-PEG-COOH, NH2-PEG-NH2, OH-PEG-COOH, OH-PEG-NH2, HCl·NH2-PEG-COOH, MAL-PEG-NHS
(3) wax ka beddelka PEG ee laanta
(mPEG)2-NHS, (mPEG)2-ALD, (mPEG)2-NH2, (mPEG)2-MAL
8. Biotinization
Biotin waxaa si xoog leh loogu xidhi karaa avidin ama streptavidin, iyo xoogga xidhidu waxay xitaa ku dhowdahay curaarta covalent.peptides-ka-calaamadeysan biotin ayaa caadi ahaan loo isticmaalaa immunoassay, histocytochemistry, iyo cytometry socodka ku salaysan fluorescence.Unugyada difaaca jirka ee la calaamadeeyay ayaa sidoo kale loo isticmaali karaa in lagu xiro peptides biotinylated.Calaamadaha biotin waxay inta badan ku xiran yihiin silsiladda dhinaca lysine ama N terminalka.6-aminocaproic acid waxaa inta badan loo isticmaalaa sida bond ka dhexeeya peptides iyo biotin.Dammaanad qaadku waa dabacsan yahay marka lagu xidho substrate-ka wuxuuna si fiican ugu xidhaa joogitaanka caqabado adag.
9. Calaamadaynta fluorescent
Calaamadaynta fluorescent waxaa loo isticmaali karaa in lagu raad raaco polypeptides ee unugyada nool iyo in la barto enzymes iyo hababka ficilka.Tryptophan (Trp) waa fluorescent, sidaas darteed waxaa loo isticmaali karaa calaamadaynta gudaha.Noocyada qiiqa ee tryptophan waxay kuxirantahay deegaanka durugsan waxayna hoos u dhigtaa hoos u dhaca dareeraha dareeraha, hanti faa'iido u leh ogaanshaha qaab dhismeedka peptide iyo xidhitaanka soo-dhoweynta.Tryptophan fluorescence waxaa demin kara aspartic acid protonated iyo glutamic acid, taas oo xaddidi karta isticmaalkeeda.Kooxda Dansyl chloride (Dansyl) waa mid aad u ifaysa marka ay ku xidhan yihiin kooxda amino waxaana inta badan loo isticmaalaa calaamadda fluorescent ee amino acids ama borotiinada.
Beddelka tamarta resonance (FRET) waxay faa'iido u leedahay daraasadaha enzymes.Marka FRET la mariyo, polypeptide substrate-ka waxa uu ka kooban yahay koox calaamadaysa fluorescence iyo koox deminaysa fluorescence.Kooxaha fluorescent ee calaamadeysan ayaa lagu demiyaa bakhtiiyaha iyada oo loo marayo wareejin tamar aan sawir lahayn.Marka peptide-ku ka go'o enzyme-ka su'aasha laga hadlayo, kooxda calaamadinta waxay sii deysaa fluorescence.
10. Cage polypeptides
Cage peptides waxay leeyihiin kooxo ilaalin indhaha laga saari karo oo ka ilaaliya peptide-ka inuu ku xidho reseptor-ka.Marka uu soo gaadho shucaaca UV, peptide-ku waa la hawlgeliyaa, isaga oo soo celinaya xidhiidhkii uu la lahaa reseptor-ka.Sababtoo ah firfircoonida indhaha waxaa lagu xakameyn karaa iyadoo loo eegayo waqtiga, baaxadda, ama goobta, peptides qafis ayaa loo isticmaali karaa in lagu barto falcelinta ka dhaca unugyada.Kooxaha ilaalinta inta badan loo isticmaalo polypeptides qafis waa kooxaha 2-nitrobenzyl iyo kuwa ka soo jeeda, kuwaas oo lagu soo bandhigi karo peptide synthesis iyada oo loo marayo derivatives amino acid ilaalinta.Astaamaha Amino acid ee la sameeyay waa lysine, cysteine, serine, iyo tyrosine.Aspartate iyo glutamate derivatives, si kastaba ha ahaatee, caadi ahaan looma isticmaalo sababtoo ah u nuglaanshahooda baaskiilka inta lagu jiro isku-dhafka peptide iyo kala-bax.
11. Polyantigenic peptide (MAP)
Peptides-ga gaaban sida caadiga ah ma aha kuwo difaac ah waana in lagu daraa borotiinnada sidayaal si ay u soo saaraan unugyada difaaca jirka.Polyantigenic peptide (MAP) wuxuu ka kooban yahay peptides isku mid ah oo badan oo ku xiran lysine nuclei, taas oo si gaar ah u muujin karta difaaca jirka ee awoodda sare leh waxaana loo isticmaali karaa in lagu diyaariyo borotiinnada-sidadaha peptide-ka.MAP polypeptides-ka waxaa lagu soo saari karaa weji adag oo ku saabsan xabagta MAP.Si kastaba ha ahaatee, isku-xidhka aan dhamaystirnayn waxay keenaysaa in la waayo ama la gooyo silsiladaha peptide ee laamaha qaarkood sidaas awgeedna ma soo bandhigaan sifooyinka MAP polypeptide-ka asalka ah.Beddel ahaan, peptides waa la diyaarin karaa oo si gooni ah loo nadiifin karaa ka dibna lagu dhejin karaa MAP.Isku xigxiga peptide ee ku xiran xudunta peptide waa mid si fiican loo qeexay oo si sahlan loo garto spectrometry mass.
Gabagabo
Wax ka beddelka Peptide waa hab muhiim ah oo lagu naqshadeeyo peptides.Peptides kiimikaad wax laga beddelay ma ilaalin karaan oo kaliya dhaqdhaqaaqa bayoolojiga sare, laakiin sidoo kale si wax ku ool ah uga fogaanayaan cilladaha difaaca jirka iyo sunta.Isla mar ahaantaana, wax ka beddelka kiimikaad wuxuu siin karaa peptides-ka qaar ka mid ah sifooyin heer sare ah oo cusub.Sanadihii la soo dhaafay, habka firfircoonida CH ee wax ka beddelka ka dib ee polypeptides ayaa si degdeg ah loo sameeyay, natiijooyin badan oo muhiim ah ayaa la gaaray.
Waqtiga boostada: Mar-20-2023