Izidakamizwa ze-peptide ngokuvamile zichazwa njengama-polymers akhiwe ngamabhondi e-amide anezinsalela ze-amino acid ezingaphansi kwama-40.Ngenxa yomsebenzi ophezulu we-receptor kanye nokukhethwa kwezidakamizwa ze-peptide ezinengozi ephansi yemiphumela emibi, kube nesithakazelo esinamandla kuma-peptide avela embonini yezemithi.Ngalesi sikhathi, bekukhona nezidakamizwa eziningi zenkanyezi, ebezigxile kakhulu embonini yezifo ze-metabolic, njenge-GLP-1 analogue somalitide, i-gastric inhibitory peptide (GIP) glucagon-like peptide-1 (GLP-1) tesiparatide nezinye ezimbili. - ama-receptor agonists.Ngaphezu kwalokho, ngokukhuphuka kwezidakamizwa ze-PDC ne-RDC.Njengamanje, izindlela zokulungiselela izidakamizwa ze-polypeptide ikakhulukazi zihlanganisa ukuhlanganiswa kwamakhemikhali nokuvutshelwa kwezinto eziphilayo.I-Biofermentation isetshenziswa kakhulu ukukhiqiza ama-peptide amade.Izinzuzo izindleko zokukhiqiza eziphansi, kodwa ukungakwazi ukwethula ama-amino acid angewona awemvelo ngokulandelana kwe-peptide kanye nokungakwazi ukwenza imihlobiso ehlukahlukene ochungechungeni lwe-peptide.Ngakho-ke, ukusetshenziswa kwayo nakho kulinganiselwe kakhulu.Izindlela zokuhlanganisa amakhemikhali zihlanganisa ukuhlanganiswa kwesigaba esiqinile kanye nokuhlanganiswa kwesigaba se-liquid.I-Solid-phase synthesis inenzuzo enkulu ngaphezu kwe-liquid-phase synthesis: uketshezi okweqile kungasetshenziselwa ukusabela ukuze kuqinisekiswe ukuhlangana okuphelele.Ama-amino acid amaningi, ama-shrinkage agents, kanye nemikhiqizo ekhiqizwayo ingasuswa ngemisebenzi yokuhlanza elula, ukugwema imisebenzi eyinkimbinkimbi yangemva kokucubungula nokuhlanza nokuthuthukisa ukusebenza kahle komsebenzi, ngakho indlela yokuhlanganiswa kwesigaba esiqinile iye yasetshenziswa kakhulu."Izinto zokusetshenziswa zamakhemikhali zokwenziwa kwama-peptide zifaka izinto zokuqala, ama-reagents, nezinyibilikisi."Ikhwalithi yabo, ikakhulukazi ikhwalithi yezinto zokuqala, ingaba nomthelela ohlukile kukhwalithi ye-API.Izinto zokuqala zibhekisela ekuphumeni okuqinisekisiwe kwe-amino acid kwe-peptide chain modified fatty acids, i-polyethylene glycol, njll. Njengezingcezu ezibalulekile zesakhiwo, zihlukaniswa njengezinto zokwakha esakhiweni se-API, esihlobene ngokuqondile nekhwalithi ye-API.Ngakho-ke, kufanele sigxile ekulawuleni indaba yokuqala.
I. Lungisa ukukhetha kwezinto zokuqala
I-ICHQ11 iphakamisa ngokusobala ukuthi uma umkhiqizo wekhemikhali othengiswa emakethe usetshenziswa njengento yokuqala eluhlaza, umfakisicelo ngokuvamile akadingi ukuxoxa ngokunengqondo kwawo.Imikhiqizo yamakhemikhali ethengiswa emakethe ngokuvamile ingasetshenziswa hhayi nje kuphela njengezinto zokuqala zemithi, kodwa futhi ingathengiswa ezimakethe ezingezona ezemithi.Izinhlanganisela ezenziwe ngokwezifiso nezihlanganisiwe azikho emikhiqizweni yamakhemikhali ethengiswa emakethe.Yize ingekho imakethe engeyona eyezokwelapha yokuvikela ama-amino acid ukuze ahlangabezane nencazelo ye-ICHQ11 yamakhemikhali athengiswa emakethe, ahlangene, ahluke ngamakhemikhali futhi acacile ngokwesakhiwo, kulula ukuwahlukanisa nokuwahlanza, futhi angahlonzwa futhi ahlolwe ngezindlela ezivamile zokuhlaziya. .Zinezakhiwo zamakhemikhali ezizinzile futhi kulula ukuzigcina, ukuthutha, nokuhlanganisa
Ii.Ukulawulwa kwezinto ezifanele kumpahla yokuqala
Ama-amino acid avikelayo okukhulunywe ngawo ngenhla afakwe esakhiweni se-API njengengxenye ebalulekile yesakhiwo, ehlobene ngokuqondile nekhwalithi ye-API.Ngakho-ke, kufanele silawule ngokuqinile okuqukethwe kokungcola kokubalulekile kokuqala, siqonde ukuguqulwa nokususwa kwalokhu kungcola enqubweni esunguliwe, futhi ekugcineni sicacise ubudlelwano phakathi kwabo nokungcola okuku-API.
Ukuqonda izinto zokuqala izidakamizwa ze-polypeptide
Okwesithathu, insalela ye-solvent in the material yokuqala
Ngokuvamile, uma kubhekwa ukucaciswa kokukhiqizwa kwesigaba esiqinile sama-peptide, inani elikhulu le-solvent lizosetshenziswa ukuhlanza inhlaka ye-peptide ngemva kokuqeda isinyathelo ngasinye sokuhlanganisa ama-amino acid kanye nokuphuma ekuvikelweni.Ama-peptide aluhlaza atholwe ngokuchoboza i-peptide resin nawo azokwenziwa yi-HPLC futhi omiswe yiqhwa.Ngakho-ke, kunengozi encane yokuthi inani elincane le-solvent elinamathiselwe kuma-amino acids avikelayo lizolethwa ku-API yokugcina.Kodwa-ke, ukunakwa okukhethekile kufanele kukhokhwe ezinsalela ze-acetate, i-butyl acetate, nezincibilikisi zotshwala, njengoba lezi zincibilikisi zingabangela imiphumela emibi ngama-amino acid asebenzayo noma amaketanga e-peptide ngesikhathi sokuhlangana okusebenzayo kwama-amino acid.Isibonelo, ngesikhathi sokuhlangana kwe-amino acid, i-acetic acid esele izosabela neqembu lama-amino eliveziwe ochungechungeni lwe-peptide, okuholela ekugcineni okuvaliwe kweketango le-peptide;Ngesikhathi sokusebenza kwe-amino acid, i-solvent esele yotshwala ingase isabelane neqembu le-carboxyl elisebenzayo, okuholela ekudlulisweni kwe-amino acid esebenzayo, ukunciphisa okulingana nama-amino acid, futhi ekugcineni kubangele ukuhlangana kwe-amino acid engaphelele kanye nokuntuleka kokungcola kwe-peptide.Inkampani ilawula i-butyl acetate, utshwala, i-methanol, ne-acetic acid ku-COA, ithatha i-amino acid evela ku-Zheng Yuan Biochemical njengesibonelo.Izinga le-butyl acetate lalingu-≤0.5% i-butyl acetate, elitholwe ukuthi lingu-0.10%.Ngokusho kwe-ICHQ3C, i-butyl acetate yezinhlobo ezintathu zezincibilikisi, ibeka izinga elingu-0.5% noma ngaphansi ngokuhambisana nezidingo ze-ICHQ3C, kodwa ukucabangela i-butyl acetate amino acetylation kungase kuholele engozini, futhi kubhekane ne-butyl acetate ukuze kumiswe ucwaningo. , ukunquma izindinganiso ezifanele kakhulu.
Isikhathi sokuthumela: Aug-29-2023