Qhov tsis ruaj tsis khov ntawm peptides yog ib qho teeb meem tseem ceeb hauv lawv cov kev tshawb fawb formulation, thiab muaj ntau qhov laj thawj rau qhov no. Tab sis tsis muaj ntau qhov laj thawj tseem ceeb rau kev tsis ruaj khov ntawm qee yam peptide. Kev kawm ntxaws ntxaws ntawm cov teebmeem ntawm sab nraud (xws li pH, qhov kub thiab txias, lub teeb, oxygen concentration, thiab lwm yam) ntawm peptide stability tuaj yeem pab tsim cov qauv tsim nyog. Txawm hais tias cov txheej txheem los ntawm cov tshuaj ntxiv stabilize peptides tseem tsis tau nkag siab tag nrho, kev siv cov additives tseem yog ib qho tseem ceeb los txhim kho kev ruaj ntseg ntawm peptide formulations. Daim ntawv thov ntawm kev tshuaj ntsuam xyuas xws li CD thiab DSC tuaj yeem pab tshawb xyuas sai rau cov khoom siv ntxiv.
Yog vim li cas rau peptide instability:
Cov tshuaj tiv thaiv Deamidation: Hauv cov tshuaj tiv thaiv deacetylation, Asn / Gln residues yog hydrolyzed los ua Asp / Glu. Cov tshuaj tiv thaiv tsis yog enzymatic deamidation yog nqa tawm. Cov pab pawg amide nyob rau hauv Asn Gly qauv yog yooj yim hydrolyzed, thiab cov amide pawg nyob rau saum npoo ntawm lub molecule kuj yooj yim hydrolyzed dua cov nyob rau hauv lub molecule.
Muaj ob lub laj thawj tseem ceeb vim li cas peptide cov kev daws teeb meem yog qhov ua rau oxidation: ib qho yog qhov paug ntawm peroxides hauv cov tshuaj, thiab lwm qhov yog oxidation ntawm peptides. Ntawm tag nrho cov amino acid residues, Met, Cys, Nws, Trp, Tyr, thiab lwm yam yog qhov yooj yim tshaj plaws oxidized. Cov pa ib nrab siab, qhov kub thiab txias, thiab cov tshuaj tsis haum kuj muaj feem cuam tshuam rau oxidation.
Hydrolysis: Peptide bonds hauv peptides yooj yim hydrolyzed thiab tawg. Peptide bonds tsim los ntawm Asp yog yooj yim dua tawg dua li lwm cov peptide bonds, tshwj xeeb tshaj yog Asp Pro thiab Asp Gly peptide bonds.
Tsim cov nyiaj disulfide tsis raug: Kev sib pauv ntawm disulfide bonds lossis ntawm disulfide bonds thiab thiol pawg tuaj yeem tsim cov disulfide daim ntawv cog lus tsis raug, ua rau muaj kev hloov pauv hauv cov qauv tertiary thiab poob ntawm kev ua haujlwm.
Racemization: Tsuas yog Gly, alpha carbon atoms ntawm tag nrho cov amino acid residues yog chiral thiab yooj yim undergo racemization tshwm sim nyob rau hauv alkaline catalysis. Ntawm lawv, Asp residues feem ntau ua rau cov tshuaj tiv thaiv racemization.
- tshem tawm: - tshem tawm yog hais txog kev tshem tawm cov pab pawg ua haujlwm ntawm - carbon atom hauv cov amino acid residues. Cys, Ser, Thr, Phe, Tyr thiab lwm yam residues tuaj yeem degraded los ntawm - tshem tawm. - Kev tshem tawm yog nquag tshwm sim ntawm alkaline pH, thiab kub thiab hlau ions kuj muaj kev cuam tshuam rau nws.
Denaturation, adsorption, aggregation, lossis nag lossis daus feem ntau muaj feem cuam tshuam rau kev puas tsuaj ntawm cov qauv tertiary thiab theem nrab. Nyob rau hauv lub xeev denatured, peptides feem ntau yog cov tshuaj lom neeg cov tshuaj tiv thaiv thiab lawv cov kev ua ub no nyuaj rau rov zoo. Nyob rau hauv tus txheej txheem ntawm peptide denaturation, intermediates yog thawj tsim. Lub solubility ntawm intermediates feem ntau yog tsawg, ua rau lawv yooj yim rau aggregate thiab tsim aggregates, uas nyob rau hauv lem daim ntawv pom precipitates rau qhov muag liab qab.
Qhov saum npoo adsorption ntawm cov protein yog lwm qhov teeb meem mob taub hau thaum lawv khaws thiab siv, xws li riL-2 adsorbing ntawm cov kav dej thaum lub sij hawm Qu perfusion, ua rau kev ua haujlwm poob.