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#Txhua tshuaj xyuas cov tshuaj insulin zoo li kev loj hlob tsim qauv peptides (iGF-des peptides)

Cov tshuaj insulin zoo li kev loj hlob (IGF) yog tus tseem ceeb piav qhia molecule uas tswj hwm cov xov tooj ntawm tes, txawv thiab metabolism. Ntawm lawv, iGF {{-1 thiab nws cov receptor (i, nws tau nyiam nyob rau hauv daim teb ntawm cov tshuaj thiab bioengineering. Txawm li cas los xij, ntuj IGF peptides muaj teeb meem xws li luv luv ib nrab-lub neej, yooj yim degradation thiab muaj peev xwm immunogenicity. ** IGF-DES (tus tsim qauv tsim tawm thiab ruaj khov) peptized ** tsim los ntawm kev hloov kho tshuaj lom neeg thiab kev txhim kho kev txhim kho lawv cov ntawv thov kev kho mob. Cov kab lus no piv tawm cov kev faib tawm, cov khoom siv dag zog thiab ua haujlwm zoo ntawm IGF-des peptides.

## 1. Kev faib tawm thiab cov yam ntxwv ntawm IGF-des peptides

### 1. ** D-amino acid hloov peptides **

- ** Tus yam ntxwv tsim qauv **: Hloov ntuj L-hom amino acids nrog daim iav isomer d-hom amino acids kom txo cov kev lees paub.

- ** ** Zoo **:

- Ua kom zoo dua rau enzymatic degradation, ntshav ib nrab-lub neej txuas mus rau 3-5 lub sij hawm uas muaj peptides.

- Txo kev txhaj tshuaj tiv thaiv Immunogenicity thiab anti-tshuaj antibody (ADA) kev tsim khoom.

- ** Lub cev thiab tshuaj lom neeg **:

- Molecular hnyav ntau yam: 7. {5-8. 5 kda (zoo ib yam li ntuj igf {4}}).

- Solubility: Maintained at >10 mg / ml ntawm physiological ph, hydrophobic amino acids hloov yuav xav kom muaj kev sib ntxiv ntawm cov cosololents.

- Xim: Dawb crystalline hmoov tom qab purification, tsis muaj xim thiab pob tshab.

- ** Tus sawv cev rau rooj plaub **: iGF-des {2}} (d-hom agwÃ, lys⁶⁸).

### 2. ** Peptides **

- ** Cov qauv nta **: Qhia cov qauv Intramolecular Cyclization los ntawm kev cuam tshuam disulfide, Amide daim ntawv cog lus lossis nyem Chemistry.

- ** ** Zoo **:

- Txhim kho kev ua txhaum cai, kho tus saib xyuas ib qho (KD) ntawm 0. {2}} nm.

- Improved thermal stability, with >90% kev ua haujlwm khaws cia tom qab 4 teev ntawm kev kho mob ntawm 60 degree.

- ** Lub cev thiab tshuaj lom neeg **:

- Molecular hnyav nce ntxiv los ntawm txog 200-400 da (nyob ntawm qhov txuas).

- isoelectric taw (PI) hloov mus rau acidity (pH 5. 5-6. 2).

- Xim: Lyophilized hmoov yuav yog daj me ntsis (vim oxidation byproducts).

- ** Txoj kev txheej txheem kev kawm ** suav nrog Head-to-Tail Cyclization thiab sab saw hneev taw-txuas (xws li Cys-Cys Disulfide Cyclization).

### 3. ** PEgylated Peptides **

- ** Cov qauv nta **: Polyethylene glycol (peg) phaus hnyav (molecular phaus (molecular phaus (molecular phaus (molecular phaus (molecular phaus (molecular hnyav {1} 【K-Terminus lossis cov Lysine seem.

- ** ** Zoo **:

- Txo lub raum cantance, thiab ib nrab-lub neej txuas rau ntau tshaj 72 teev.

- Tseem ceeb tiv thaiv kab mob tiv thaiv kab tiv thaiv, nrog ADA qhov xwm txheej ntawm<1%.

- ** Lub cev thiab tshuaj lom neeg **:

- Qhov tseem ceeb tshaj plaws nyob rau hauv molecular hnyav (15-50 kda), xav kom muaj ultrafiltration purification.

- Improved solubility (>50 mg / ml), tab sis colloidal argregation yuav ua.

- Xim: mis nyuj dawb colloidal daws tom qab pgylation.

- ** Cov nyom **: Yuav tsum ua kom zoo PEG saw Saw thiab txuas qhov chaw kom tsis txhob tiv thaiv cov xaib.

### 4. ** Glycosylated / Sulfated Peptides **

- ** QAUV NTAU HOM **: QHIA TXOG Cov kab lus qab zib (xws li Mannose, sialic acid) lossis cov khoom siv sulfate.

- ** ** Zoo **:

- Txhim kho lub hom phiaj, cov ntaub so ntswg tshwj xeeb cov khoom plig los ntawm cov protein ntau (xws li Hepatocyte asialChoplecoplecoplecoplecoplectin

- AnticoMulant nyhuv (sulfated hom).

- ** Lub cev thiab tshuaj lom neeg **:

- Glycosylation ua rau 30-50% nce hauv molecular hnyav.

- Txhim kho qhov tseem ceeb hydrophilicity, txo qis isoelectric taw tes rau ph 4. 0-4. 5.

- Xim: Glycosylation cov khoom yog feem ntau lub teeb xim av (los ntawm cov tshuaj tiv thaiv maillard).

- ** ** DAIM NTAWV THOV NYIAJ RAUG ***: Lub siab-kev ua yeeb yam tshuaj tiv thaiv tshuaj, kev kho mob tsis tiv thaiv kev tiv thaiv.

## 2. Cov tswv yim txhim kho rau cov khoom siv lub cev thiab tshuaj lom neeg ntawm iigf-des peptides

### 1. ** Ua kom muaj kev ruaj khov "

- **Temperature tolerance**: Cyclic IGF-DES retains >95% kev ua si tom qab 6 lub hlis ntawm kev cia ntawm 4 degree, uas yog qhov zoo dua li 60% ntawm cov neeg peptides.

- ** PHI PHEM **: Cov nqi degradation ntawm D-hloov pauv peptides hauv paistric acid ib puag ncig (PH 2 0) yog<5% in 2 hours, which is suitable for oral formulation development.

## 2. ** solubility thiab tsim kev sib haum xeeb **

- ** OCE ANGIT COSPULLY PARCH (PI 5. {{{} → → 4.2) los ntawm hloov glutamic acid kom tsis txhob muaj cov pa nag.

- ** Cosvent system **: Pegylated peptides yog soluble nyob rau hauv 5% ethanol / li qub qab ntsev / ib txwm saline, haum rau kev txhaj tshuaj.

### 3. ** Optical cov yam ntxwv thiab kev tswj hwm zoo **

- ** UV nqus lub ncov nqus Peak **: Ntuj IGF muaj kev nqus tau zoo ntawm 280 tus neeg (Tyr / Phe), thiab kev hloov kho Cycloization yuav ua rau kev hloov pauv liab (± 5 nm).

- ** Fluorescence Lelling **: Cy {{{1} igf-des yog siv rau hauv Vivo kev yees duab, muaj kev vam meej / Emission Wavelengths ntawm 650/670 nm.

## 3. Daim ntawv thov cov chaw thiab chaw kuaj mob

### 1. ** Kev kho mob metabolic **

- ** Kojental mob ntshav qab zib **: Cyclic IGF-Des Gel npaj txhawb nqa cov neeg kho kom zoo los ntawm 40% (Theem II Kho Mob Sim Cov Ntaub Ntawv).

### 2. ** Kev tawm tsam kev laus thiab cov tshuaj kho mob "

- ** Kho cov tawv nqaij **: Pegylated iGF-DE microedle hloov chaw, collagen synthesis nce los ntawm cov qauv vitro).

### 3. ** Quarum tsom Kho Kev Kho **

- ** ** "Fifefition conjugate **: iGF-Des Fused nrog anti-antibody, ic₅₀ ntawm inhiber cancer mis proliferation nce mus txog 10 nm.

## 4. Cov lus qhia thiab yav tom ntej

- ** Daim thev naus laus zis thev naus laus zis **: Crispr-Cas {2} Pab cov poov xab qhia system kom ua tiav lub xaib-tshwj xeeb glycosylation.

- ** Ai-tsav tsim **: Zoo tshaj plaws Cychlization ntawm kev xaiv raws li kev twv ua AlphafoldE2 conformation.

- ** Cov txheej txheem ntsuab ntsuab **: Cov kuab-dawb khoom theem xwm txheej ua rau ib puag ncig ib puag ncig.

## Xaus

IGF-des peptide tau tawg los ntawm daim ntawv thov blockleneck ntawm ntuj igf los ntawm ntau yam kev ua lag luam txawv teb chaws. Nyob rau hauv lub neej yav tom ntej, nrog kev sib koom ua ke ntawm ntau cov thev naus laus zis thev naus laus zis, lub cim tshiab ntawm kev txawj ntse hauv kev hloov tshuaj.