Tshuaj peptide

Tshuaj peptides yog ib chav kawm ntawm cov tebchaw uas muaj cov amino acids txuas los ntawm peptide bonds, feem ntau muaj 2 txog 50 amino acids, tsim los siv los kho cov tshuaj. Lawv poob ntawm cov tshuaj me me molecule tshuaj (molecular hnyav<500 Da) and large molecule biological drugs (such as antibodies, molecular weight>10000 Da), thiab yog ib pawg tseem ceeb ntawm cov tshuaj.
 

Core nta thiab qhov zoo:
1. Muaj kev tshwj xeeb thiab muaj zog: cov tshuaj Peptide tuaj yeem xaiv khi rau lub hom phiaj (xws li receptors thiab enzymes) zoo li ntuj ligands (xws li cov tshuaj hormones thiab cytokines), yog li lawv feem ntau muaj cov teebmeem kev kho mob thiab cov kev mob tshwm sim me me.
2. Kev nyab xeeb zoo: Peptides thaum kawg metabolized rau hauv cov amino acids hauv lub cev, feem ntau tsis muaj tshuaj lom, thiab cov metabolites tsis muaj teeb meem.
3. Ntau hom kev tsim: Los ntawm kev npaj thiab sib txuas cov amino acid sequences, peptides nrog cov qauv spatial tshwj xeeb thiab kev ua haujlwm tuaj yeem tsim los rau cov hom phiaj "tsis yog tshuaj" uas nyuaj rau cov tshuaj me me los ua.
 

Cov teeb meem tseem ceeb:
1. Tsis yooj yim rau kev tswj hwm qhov ncauj: Nws yooj yim degraded los ntawm enzymes hauv plab hnyuv thiab nyuaj rau absorbed los ntawm txoj hnyuv phab ntsa.
2. Tsis zoo plasma stability: yooj yim hydrolyzed los ntawm proteases nyob rau hauv cov ntshav, ua rau ib tug luv luv ib nrab- lub neej.
3. Tsawg membrane permeability: Nws yog feem ntau nyuaj rau nkag mus rau hauv lub cell membrane, yog li nws tsuas yog ua rau lub hom phiaj ntawm lub xov tooj ntawm tes (xws li GPCRs, ion channels).
Txhawm rau kov yeej cov teeb meem no, kev txhim kho tshuaj feem ntau siv cov tswv yim xws li kev hloov kho tshuaj (xws li PEGylation, fatty acid chain modification, cyclization, introduction of D-}amino acids), cov tshuab xa tshuaj tshiab (xws li txhaj tshuaj, inhalers, transdermal thaj ua rau thaj), thiab kev txhim kho cov tshuaj peptide ua ke.
 

Cov pawg tseem ceeb thiab cov piv txwv ntawm cov tshuaj peptides
Qee qhov hnyav hnyav lossis tus neeg sawv cev tshuaj peptides cais los ntawm kev kho mob:
1. Cov kab mob metabolic teb
Ib qho kev vam meej tshaj plaws ntawm cov tshuaj peptide.
Glucagon zoo li peptide-1 receptor agonist:
· Liraglutide,semaglutide, dulaglutide: Cov no yog GLP-1 analogs uas qhib GLP-1 receptors los txhawb cov insulin secretion, inhibit glucagon secretion, qeeb plab hnyuv, thiab txo qis qab los noj mov hauv cov piam thaj hauv cov ntshav. Nws yog siv los kho mob ntshav qab zib hom 2 thiab rog rog. Simeglutide (lub npe lag luam Wegovy / Ozempic) yog tam sim no ib qho ntawm cov tshuaj uas muaj kev saib xyuas zoo tshaj plaws.

Semaglutide yog qhov ntev - ua yeeb yam, xaiv, sib tw GLP-1R agonist uas tuaj yeem nkag mus rau hauv cov hlab ntsha-hlwb barrier. Semaglutide activates GLP-1R los txhawb cov insulin secretion, inhibit plab hnyuv plab thiab qab los noj mov, thaum txhim kho autophagy, inhibiting oxidative kev nyuaj siab thiab apoptosis. Semaglutide kuj tswj hwm mitochondrial muaj nuj nqi thiab lipid metabolism (xws li txo de novo rog ntau lawm hauv daim siab). Semaglutide muaj cov dej num xws li txo cov ntshav qab zib, poob phaus, neuroprotection (xws li kev txhim kho lub cev muaj zog hauv Parkinson tus kab mob qauv, txo cov alpha synuclein aggregation), thiab txhim kho hepatic steatosis. Semaglutide tuaj yeem siv rau hauv kev tshawb fawb ntawm cov kab mob neurodegenerative thiab kab mob siab, xws li

Hom 2 mob ntshav qab zib mellitus, rog rog, Parkinson's disease, metabolism ntsig txog fatty siab kab mob (MASLD), thiab mob qog noj ntshav.

Kev tshawb nrhiav hauv vitro
1. Anti A 25-35 raug mob sim: Semaglutide (1-100 nM; 24 h) ua rau kom muaj sia nyob ntawm SH-SY5Y hlwb, nce kev qhia ntawm autophagy ntsig txog cov proteins xws li LC3II, Atg7, Beclin-1, thiab P62, inhibited Bax thiab upregulated phagy, inhibiting Bcl. apoptosis, thiab tiv thaiv cov paj hlwb.
2. Qhov ncauj squamous cell carcinoma (OSCC) kev sim ntawm tes: Semaglutide (5-40 μ M; 48 h) koob tshuaj nyob ntawm inhibits kev loj hlob, kev tsiv teb tsaws, thiab ntxeem tau ntawm Cal27 thiab HSC4 hlwb, upregulates E-cadherin thiab downregulates Vimentin38AP, activates txoj kev (nce p-P38 qhia), thiab induces cell apoptosis.
 

Hauv kev tshawb nrhiav vivo
Thaum ua cov kev sim tsiaj, kev txhaj tshuaj subcutaneous lossis intraperitoneal tuaj yeem xaiv.
Transplanted qog qauv ntawm qhov ncauj squamous cell carcinoma (OSCC)
Semaglutide (3 μ mol / kg; txhaj tshuaj subcutaneous; 3 zaug hauv ib lub lis piam; 3 lub lis piam) cuam tshuam cov qog loj hlob hauv qhov liab qab nas qhov ncauj squamous cell carcinoma (OSCC) xenograft qauv, downregulated proliferation markers Ki67 thiab PCNA, upregulated pro apoptotic protein Bax thiab downregulated anti xclL thiab protein ntau. induced qog cell apoptosis los ntawm activating P38 MAPK txoj kev.
Mob MPTP ua rau tus mob Parkinson tus qauv
Semaglutide (25 nmol / kg; intraperitoneal txhaj; Ib zaug txhua 2 hnub; 30 hnub) txhim kho MPTP ntev ua rau tus kab mob Parkinson tus qauv thiab nws lub cev tsis ua haujlwm hauv cov nas, nce tus naj npawb ntawm tyrosine (TH) zoo neurons nyob rau hauv substantia nigra, txo qis alpha synuclein aggregation ntawm cell thiab oxidative kev nyuaj siab. marker 4-HNE.
Metabolic dysfunction txuam fatty siab kab mob (MASLD) qauv
Semaglutide (25 μ g / kg / lub lis piam+100 μ g / kg / lub lis piam; Subcutaneous txhaj; Ib zaug ib lub lim tiam; Nyob rau hauv lub metabolic dysfunction txuam fatty siab kab mob (MASLD) qauv ntawm nas ntawm 11 lub lis piam, qhov hnyav, ntshav qabzib, thiab ntshav siab enzymes (ALT, AST, hepatic deposition) tau txo triglycated, hecer deposition. steatosis thiab hepatocyte ballooning tau txhim kho, thiab de novo adipogenic cov cim Acaca thiab Scd1 raug txo qis.
Insulin thiab nws cov analogues:
· Insulin aspart, insulin detec thiab insulin tegu: hloov kho cov tshuaj insulin los ntawm cov noob caj noob ces, hloov nws lub sijhawm pib thiab lub sijhawm ua haujlwm, thiab muab kev tswj cov ntshav qabzib ntau dua thiab ruaj khov rau cov neeg mob ntshav qab zib.

2. Hauv kev kho mob qog noj ntshav
· Peptide receptor radionuclide therapy:
· Lutetium-177 DOTATATE: Siv rau kev kho mob ntawm plab hnyuv thiab pancreatic neuroendocrine hlav zoo rau somatostatin receptors. Peptides (DOTATATE) ua haujlwm ua "navigation system" tsom cov qog hlwb, nqa cov xov tooj cua isotopes (lutetium 177) ua "warheads" los tua cov hlwb.
Cytotoxic conjugate peptides:
· Miqin peptide: lub cell phab ntsa peptide encapsulated nyob rau hauv liposomes, siv rau kev kho mob ntawm non metastatic osteosarcoma, uas yuav qhib tau macrophages mus tua cov qog.
· Lub hom phiaj kho peptides:
· Kaffizomib: ib qho proteasome inhibitor (hloov tetrapeptidyl ketone) siv los kho ntau yam myeloma.
3. Kab mob plawv
· Brain natriuretic peptide analog: Nasilide: recombinant tib neeg B-hom natriuretic peptide, siv rau kev kho mob hauv cov hlab ntsha ntawm lub plawv tsis ua hauj lwm decompensated, tuaj yeem nthuav cov hlab ntsha, txhawb kev tso zis, thiab txo cov plawv dhia.
· Anticoagulant peptide: Bivalirudin: ib qho ncaj qha thrombin inhibitor (20 amino acids) siv los tiv thaiv coagulation hauv percutaneous coronary intervention therapy.
4. Antibacterial teb
· Antimicrobial peptides lossis peptide tshuaj tua kab mob:
· Daptomycin: tshuaj tua kab mob cyclic peptide uas tua cov kab mob Gram zoo, suav nrog methicillin- tiv taus Staphylococcus aureus, los ntawm kev cuam tshuam cov membrane muaj peev xwm ntawm cov kab mob.
· Polymyxin B/E: tshuaj tua kab mob peptide uas yog ib qho ntawm "kab kawg ntawm kev tiv thaiv" tshuaj rau kev kho cov kab mob tshwm sim los ntawm multidrug -cov kab mob Gram tsis zoo xws li Acinetobacter baumannii thiab Pseudomonas aeruginosa.
5. Endocrine thiab kev ua me nyuam
· Gonadotropin tso cov tshuaj hormones analogs:
Leuprorelin thiab Goserelin: GnRH agonists. Kev siv sijhawm ntev tuaj yeem cuam tshuam qhov tso tawm ntawm pituitary gonadotropin, uas yog siv los kho mob qog noj ntshav prostate, mob cancer mis, endometriosis thiab central precocious puberty.
Somatostatin analogues:
· Octreotide thiab Lantreotide: Siv los tswj cov tsos mob ntawm acromegaly thiab kho cov kab mob ntsig txog plab hnyuv, pancreatic, neuroendocrine hlav (xws li carcinoid syndrome).
6. Nyob rau hauv cov kab mob skeletal
· Parathyroid hormone analogues:
· Teriparatide thiab Abalotide: yog cov khoom tawg ntawm PTH lossis nws cov peptides cuam tshuam uas tuaj yeem txhawb kev tsim cov pob txha thiab siv los kho cov pob txha loj.
7. Diagnostic reagents
· Radioactive sau npe peptides:
· Gallium-68 DOTATATE/DOTATOC: Siv rau positron emission tomography imaging thiab localization diagnosis ntawm neuroendocrine hlav qhia somatostatin receptors.

Cov tshuaj peptides tau dhau los ua ib feem tseem ceeb ntawm kev txhim kho tshuaj niaj hnub no vim lawv cov kev xaiv siab, ua tau zoo, thiab kev nyab xeeb zoo. Nrog rau kev txhim kho sai ntawm cov thev naus laus zis xws li qhov ncauj peptides, peptide ua ke cov tshuaj, bifunctional / multifunctional peptides, thiab peptide tsim raws li cov khoos phis tawj thiab AI, daim ntawv thov kev cia siab ntawm cov tshuaj peptides yuav ntau dua. Lawv loj hlob los ntawm "hauv nruab nrab" nruab nrab ntawm cov tshuaj me me thiab cov tshuaj biomacromolecule mus rau ib pawg tshuaj tseem ceeb uas tuaj yeem tsom cov kab mob refractory thiab muaj cov txiaj ntsig zoo.