Kunzwisisa kwe polypeptide zvinodhaka kutanga zvinhu

Mishonga yePeptide inowanzotsanangurwa semapolymer anoumbwa nemaamide bond ane mashoma pane makumi mana amino acid masara.Nekuda kwechiitiko chepamusoro chekugamuchira uye kusarudzwa kwemishonga yepeptide ine njodzi yakaderera yemhedzisiro, kwakave nekufarira kwakasimba mumapeptide kubva kuindasitiri yemishonga.Munguva iyi, kwaivewo nemishonga yakawanda yenyeredzi, iyo yainyanya kunyura muindasitiri yechirwere chemetabolic, senge GLP-1 analogue somalitide, gastric inhibitory peptide (GIP) glucagon-like peptide-1 (GLP-1) tesiparatide uye mamwe maviri maviri. - receptor agonists.Mukuwedzera, nekukwira kwePDC uye RDC mishonga.Parizvino, nzira dzekugadzirira dzemishonga yepolypeptide dzinonyanya kusanganisira makemikari synthesis uye biological fermentation.Biofermentation inonyanya kushandiswa kugadzira peptides refu.Zvakanakira mutengo wakaderera wekugadzira, asi kutadza kuunza asiri echisikigo amino acids mupeptide kutevedzana uye kusakwanisa kuita zvakasiyana siyana zvekushongedza pa peptide cheni.Naizvozvo, kushandiswa kwayo kwakaganhurirwawo zvikuru.Chemical synthesis nzira dzinosanganisira solid phase synthesis uye liquid phase synthesis.Solid-phase synthesis ine mukana wakakura pamusoro pemvura-chikamu synthesis: yakawandisa yezvinhu inogona kushandiswa kuita kuti ive nechokwadi chekubatana.Yakawandisa amino acids, shrinkage agents, uye ne-zvigadzirwa zvinogona kubviswa nekuita nyore kuchenesa, kudzivirira yakaoma post-processing uye kuchenesa mashandiro uye kuvandudza kushanda zvakanaka, saka iyo solid-phase synthesis nzira yave yakanyanya kushandiswa."Chemical synthesis mbishi yekugadzira peptides inosanganisira yekutanga zvinhu, reagents, uye zvinonyungudutsa."Hunhu hwavo, kunyanya kunaka kwezvinhu zvekutanga, zvinogona kuita zvakasiyana pamhando yeAPI.Zvinyorwa zvekutanga zvinonyanya kureva zvakavimbiswa amino acid derivatives ye peptide chain modified fatty acids, polyethylene glycol, etc. Sezvimedu zvakakosha zvekugadzirisa, zvinorondedzerwa sezvinhu zviri muhutano hweAPI, iyo inoenderana zvakananga nehutano hweAPI.Nokudaro, tinofanira kutarisa pakutonga kwezvinhu zvekutanga.

多肽药物起始物料

I. Rongedzera kusarudzwa kwezvinhu zvekutanga

ICHQ11 inonyatso kurudzira kuti kana chigadzirwa chemakemikari chinotengeswa pamusika chikashandiswa sechinhu chekutanga, munyoreri haawanzo kuda kukurukura zvine musoro.Zvigadzirwa zvemakemikari zvinotengeswa pamusika kazhinji zvinogona kushandiswa kwete sekutanga zvinhu zvemishonga, asi zvakare zvinogona kutengeswa mumisika isiri yemishonga.Makemikari akagadzirwa uye akagadzirwa haasi emakemikari anotengeswa pamusika.Kunyangwe pasina musika usiri wemushonga wekuchengetedza amino acids kuti asangane neICHQ11 tsananguro yemakemikari anotengeswa pamusika, iwo akabatana, ane makemikari akasiyana uye akajeka muchimiro, ari nyore kuzviparadzanisa uye kuchenesa, uye anogona kuzivikanwa nekuedzwa nenzira dzakajairika dzekuongorora. .Ivo vane yakagadzikana makemikari zvimiro uye zviri nyore kuchengeta, kutakura, uye synthesize

Ii.Kudzora kwezvinhu zvakakosha mune yekutanga zvinhu

Izvo zvambotaurwa zvinodzivirira amino acids zvinosanganiswa mu API chimiro sechinhu chakakosha chekugadzirisa chikamu, icho chakanangana nemhando ye API.Nokudaro, tinofanira kudzora zvakasimba kusvibiswa kwemukati muzvinyorwa zvekutanga, kunzwisisa kushandurwa uye kubviswa kwezvisina kuchena izvi muhutano hwakagadzwa, uye pakupedzisira kujekesa hukama huri pakati pavo uye tsvina muAPI.

Kunzwisisa kwe polypeptide zvinodhaka kutanga zvinhu

Chechitatu, iyo inonyungudutsa inosara mune yekutanga zvinhu

Kazhinji, kupihwa iyo chaiyo yechikamu chakasimba chizvarwa chepeptides, yakawanda solvent ichashandiswa kuchenesa peptide resin mushure mekupedza nhanho imwe neimwe yeamino acid coupling uye kudzivirirwa kubva padziviriro.Crude peptides inowanikwa nekutsemura peptide resin ichagadzirwawo neHPLC uye yakaomeswa nechando.Nokudaro, pane ngozi shoma yokuti iyo shoma shoma yakasungirirwa kune inodzivirira amino acids ichaendeswa kune yekupedzisira API.Nekudaro, kunyanya kutariswa kunofanirwa kubhadharwa kune zvakasara zveacetate, butyl acetate, uye doro zvinonyungudutsa, sezvo izvi zvinonyungudutsa zvinogona kukonzera mhedzisiro neanoshanda amino acids kana peptide cheni panguva inoshanda kubatanidza amino acids.Semuenzaniso, panguva yekubatanidza amino acid, iyo yakasara acetic acid ichaita neboka reamino rakafumurwa pacheni yepeptide, zvichikonzera kupera kwakavharwa kweketani yepeptide;Munguva yeamino acid chiitiko, iyo yakasara doro solvent inogona kuita neiyo inoshanda carboxyl boka, zvichitungamira mukupfuura kweamino acid inoshanda, kuderedza yakaenzana neamino acid, uye pakupedzisira zvichikonzera kusakwana kweamino acid kubatana uye kushomeka kwepeptide tsvina.Iyo kambani inodzora butyl acetate, doro, methanol, uye acetic acid muCOA, ichitora amino acid kubva kuZheng Yuan Biochemical semuenzaniso.Muyero webutyl acetate waiva ≤0.5% butyl acetate, iyo yakanyatsoonekwa kuva 0.10%.Zvinoenderana neICHQ3C, butyl acetate yemhando nhatu dzezvinonyungudutsa, isa mwero we0.5% kana zvishoma zvinoenderana nezvinodiwa zveICHQ3C, asi kufunga nezve butyl acetate amino acetylation kunogona kutungamira kune njodzi, zvakare kubata nebutyl acetate kumisikidza tsvakurudzo. , kusarudza imwe mipimo yakakodzera.


Nguva yekutumira: Aug-29-2023