Gusobanukirwa ibikoresho byo gutangiza imiti ya polypeptide

Imiti ya peptide isobanurwa muri rusange nka polymers igizwe na amide ihuza ibisigisigi bitarenze 40 bya aside amine.Bitewe nibikorwa byinshi byo kwakira no guhitamo imiti ya peptide ifite ibyago bike byingaruka mbi, habaye inyungu nyinshi kuri peptide ziva mu nganda zimiti.Muri kiriya gihe, hari kandi ibiyobyabwenge byinshi byinyenyeri, byibanze cyane mubikorwa byindwara ziterwa na metabolike, nka GLP-1 analogue somalutide, gastric inhibitory peptide (GIP) glucagon imeze nka peptide-1 (GLP-1) tesiparatide nizindi ebyiri -kwakira agoniste.Mubyongeyeho, hamwe no kwiyongera kwibiyobyabwenge bya PDC na RDC.Kugeza ubu, uburyo bwo gutegura imiti ya polypeptide burimo ahanini synthesis ya chimique na fermentation ya biologiya.Biofermentation ikoreshwa cyane cyane kubyara peptide ndende.Ibyiza nibiciro byumusaruro muke, ariko kudashobora kwinjiza aside amine idasanzwe muburyo bwa peptide no kudashobora gukora imitako itandukanye kumurongo wa peptide.Kubwibyo, ikoreshwa ryayo naryo rigarukira cyane.Uburyo bwa synthèse chimique burimo synthesis ikomeye ya synthesis hamwe na synthesis ya fase.Synthesis-fonction synthesis ifite inyungu zingenzi kurenza synthesis-fonction synthesis: ibirenze ibikoresho birashobora gukoreshwa mubitekerezo kugirango habeho guhuza byuzuye.Kurenza aminide acide, kugabanya ibikoresho, nibindi bicuruzwa birashobora gukurwaho nibikorwa byogusukura byoroshye, ukirinda ibikorwa bigoye nyuma yo gutunganya no kweza no kunoza imikorere, bityo rero uburyo bukomeye bwa synthesis bwakoreshejwe cyane.“Sintezike ya chimique ibikoresho fatizo byo guhuza peptide harimo ibikoresho byo gutangiza, reagent, hamwe na solde.”Ubwiza bwabo, cyane cyane ubwiza bwibikoresho byambere, burashobora kugira ingaruka zitandukanye kumiterere ya API.Ibikoresho byo gutangira bivuga cyane cyane inkomoko ya aminide yemewe ya peptide yumunyu wa peptide wahinduwe na acide fatty, polyethylene glycol, nibindi nkibice byingenzi byubatswe, bishyirwa mubikorwa nkibikoresho muburyo bwa API, bifitanye isano itaziguye nubwiza bwa API.Kubwibyo, dukwiye kwibanda ku kugenzura ibikoresho byo gutangira.

I. Shyira mu gaciro guhitamo ibikoresho byambere

ICHQ11 isobanura neza ko niba ibicuruzwa bivura imiti bigurishwa ku isoko bikoreshwa nkibikoresho fatizo byambere, usaba adakeneye kuganira ku mpamvu yabyo.Ibicuruzwa bivura imiti bigurishwa ku isoko muri rusange ntibishobora gukoreshwa gusa nkibikoresho byo gutangiza imiti, ariko birashobora no kugurishwa ku masoko atari imiti.Ibikoresho byahinduwe kandi bihujwe ntabwo ari ibya chimique igurishwa ku isoko.Nubwo nta soko ridafite imiti irinda aside amine kugira ngo ryuzuze ibisobanuro bya ICHQ11 by’imiti igurishwa ku isoko, biroroshye, bitandukanye mu buryo bwa shimi kandi byubatswe mu buryo bworoshye, byoroshye gutandukanya no kweza, kandi birashobora kumenyekana no kugeragezwa hakoreshejwe uburyo rusange bwo gusesengura. .Bafite imiti ihamye kandi yoroshye kubika, gutwara, no guhuza

Ii.Kugenzura ibintu bijyanye nibikoresho byo gutangira

Acide aminide acide yavuzwe haruguru yinjijwe muburyo bwa API nkigice cyingenzi cyubatswe, gifitanye isano itaziguye nubwiza bwa API.Kubwibyo, dukwiye kugenzura byimazeyo ibirimo umwanda mubikoresho byambere, tugasobanukirwa ihinduka nogukuraho ibyo byanduye mugihe cyagenwe, hanyuma amaherezo tugasobanura isano iri hagati yabo n’umwanda muri API.

Gusobanukirwa ibikoresho byo gutangiza imiti ya polypeptide

Icya gatatu, ibisigara bisigaye mubikoresho byambere

Muri rusange, ukurikije umwihariko wo kubyara icyiciro cya peptide, hazakoreshwa umubare munini wa solide nyuma yo kurangiza buri ntambwe yo guhuza aside amine no gutandukana kurinda.Peptide ya peteroli yabonetse mugukata peptide resin nayo izakorwa na HPLC hanyuma ikonje.Rero, harikibazo gike cyuko umubare muto wa solvent wometse kuri acide irinda amine uzashyikirizwa API yanyuma.Icyakora, hakwiye kwitabwaho byumwihariko ibisigisigi bya acetate, butyl acetate, hamwe nudukoko twa alcool, kuko iyi miti ishobora gutera ingaruka mbi hamwe na acide amine cyangwa iminyururu ya peptide mugihe cyo guhuza aside amine.Kurugero, mugihe cyo guhuza aside amine, aside asike isigaye izitwara hamwe nitsinda rya amino ryerekanwe kumurongo wa peptide, bikaviramo iherezo rya peptide;Mugihe cyibikorwa bya aside amine, ibisigisigi bya alcool bisigaye bishobora kwitwara hamwe nitsinda rya carboxyl rikora, biganisha kuri passivasi ya aside amine ikora, bikagabanya ihwanye na aside amine, hanyuma bikaviramo guhuza aside amine ituzuye no kubura umwanda wa peptide.Isosiyete igenzura butyl acetate, inzoga, methanol, na acide acike muri COA, ifata urugero rwa aside amine muri Zheng Yuan Biochemical.Ibipimo bya acetate ya butyl yari ≤0.5% ya butyl acetate, byagaragaye ko ari 0,10%.Nk’uko ICHQ3C ibivuga, butyl acetate yubwoko butatu bwumuti, shiraho igipimo cya 0.5% cyangwa munsi yacyo ukurikije ibisabwa na ICHQ3C, ariko urebye butyl acetate amino acetylation ishobora gutera ibyago, ikanakorana na butyl acetate kugirango uburinganire bwubushakashatsi , kugirango umenye ibipimo bikwiye.