Liphetoho tsa Peptide
Peptide Pegylation
Peptide Pegylation ke eng?
Peptide polyethylene glycolisation ke mokhoa oa ho kopanya polyethylene glycol e le 'ngoe kapa ho feta. (PEG) liketane ho molek'hule ea peptide. Polyethylene glycolisation e eketsa boima ba molek'hule ea peptide, e sireletsa peptide ho tloha hydrolysis ka protheine hydrolases, 'me qetellong e ntlafatsa pharmacokinetics ea peptide.
Li-peptide li bapala karolo ea bohlokoa indastering ea meriana le nts'etsopele ea kalafo ea lithethefatsi. Leha ho le joalo, ts'ebeliso ea in vivo ea li-peptide e lekanyelitsoe ka lebaka la ho senyeha ka potlako ke li-enzyme tsa proteolytic, ho qhibiliha ho fokolang, liketso tsa antigen, le ho sefa ha glomerular liphio. Khokahano e kholo ea polyethylene glycol (PEG) e fokotsa immunogenicity, e ntlafatsa ho qhibiliha le ho fokotsa ho hloekisoa ha renal. Ho eketsoa ha liketane tsa PEG tsa monodisperse ke ntlha ea bohlokoa ntlafatsong ea kalafo ea li-peptide tsa PEGylated.. Li-peptide tsena tse sireletsehileng le tse sebetsang tsa polyethylene glycolated li bohlokoa bakeng sa katleho e nepahetseng ea kalafo..
Bo-rasaense ba Peptide Pegylation
Lihokelo tse tloaelehileng tsa PEG le likhutsufatso
·Tobetsa Chemistry, e etsahalang pakeng tsa sehlopha sa azide sa reagent ea PEG le sehlopha sa alkyne sa peptide, kapa ka tsela e fapaneng.
·Suzuki-Miyaura Coupling, e etsahalang lipakeng tsa sehlopha sa iodophenyl sa PEG reagent le sehlopha sa aryl boronic acid sa peptide., kapa ka tsela e fapaneng..
·Sonogashira Coupling, e etsahalang lipakeng tsa sehlopha sa iodophenyl sa reagent ea PEG le sehlopha sa alkyne sa peptide., kapa ka tsela e fapaneng.
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Abbrev.
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Lebitso le felletseng la PEG Chain
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PEG |
tetraethylene glycol |
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mini-PEG2 |
8-amino-3,6-dioxaoctanoic acid |
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mini-PEG3 |
amino-3,6,9-trioxaundecanoic acid |
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NH2-PEG2-acid |
3-(2-(2-Aminoethoxy)ethoxy)-asiti ea propanoic |
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PEG750 |
Poly(ethylene glycol) methyl ether (karolelano Mn 750) |
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PEG1000 |
Poly(ethylene glycol) methyl ether (karolelano Mn 1000) |
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PEG2000 |
Poly(ethylene glycol) methyl ether (karolelano Mn 2000) |
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PEG5000 |
Poly(ethylene glycol) methyl ether (karolelano Mn 5000) |
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Ester (OTBzl) |
P-Nitroanilide |
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KLH (-COOH ea C terminal) |
tBu |
Litlhaloso tse hlahang
Nts'etsopele ea Radiolabeled Irreversible Peptide Ligand bakeng sa PET Imaging ea Vascular Endothelial Growth Factor.
Lisebelisoa tsa litšoantšo tse thehiloeng ho li-peptide probes li na le thepa e lakatsehang ea pharmacokinetic ha feela li na le kamano e phahameng bakeng sa sepheo sa tsona sa vivo.. Mokhoa oa ho ntlafatsa kamano ea peptide ligand bakeng sa sepheo sa eona ke ho etsa hore tšebelisano ena e be e kopaneng le e ke keng ea fetoloa.. Bakeng sa morero ona, re ile ra lekola tag ea 64Cu e ngotsoeng affinity peptide, 64Cu-L19K-(5-fluoro-2,4-dinitrobenzene) (64Cu-L19K-FDNB), e tlamang ka kopanelo le ka mokhoa o ke keng oa fetoloa ho vascular endothelial growth factor (VEGF) joalo ka moemeli oa litšoantšo oa PET. Re bapisitse thepa ea in vivo ea 64Cu-L19K-FDNB ho VEGF-e bonts'ang tumor xenografts le li-analog tsa eona tse sa tlameng., 64Cu-L19K-(2,4-dinitrophenyl) (64Cu-L19K-DNP) le 64Cu-L19K. Mekhoa: Peptide ea L19K (GGNECDIARMWEWECFERK-CONH2) e hahiloe ka 1,4,7-triazacyclononane-1,4,7-triacetic acid sebakeng sa N terminus bakeng sa radiolabeling le 64Cu ka polyethylene glycol spacer pakeng tsa peptide le chelate.. 1,5-difluoro-2,4-dinitrobenzene e kopantsoe ho C-terminal lysine bakeng sa ho hokahanya le VEGF., e bakang L19K-FDNB. 64Cu-L19K-FDNB e ile ea lekoa bakeng sa tlamo e kopanetsoeng ho VEGF in vitro. E le taolo, L19K e kopantsoe ho 1-fluoro-2,4-dinitrobenzene, e bakang L19K-DNP. PET imaging le lithuto tsa biodistribution tsa 64Cu-L19K-FDNB, 64Cu-L19K-DNP, le matsoalloa a 64Cu-L19K a bapisoa le xenografts ea HCT-116. Lithuto tse thibelang tsa 64Cu-L19K-FDNB li entsoe ka kopanelo ea ho fetella ho sa ngolisoang L19K-FDNB. Liphetho: Lithuto tse tlamang tsa in vitro li netefalitse tlamo e kopanetsoeng le e ke keng ea fetoloa ea 64Cu-L19K-FDNB ho VEGF., athe 64Cu-L19K-DNP le 64Cu-L19K li ne li sa tlame ka kopanelo. Litšoantšo tsa PET li bonts'itse ho ts'oaroa ha hlahala e phahameng ka 64Cu-L19K-FDNB ho feta ka 64Cu-L19K-DNP le 64Cu-L19K, e nang le litekanyetso tse tloaelehileng tsa ho amohela tsa 0.62 ± 0.05, 0.18 ± 0.06, le 0.34 ± 0.14, ka ho latellana, ho 24 h ka mor'a ente (P < 0.05), le 0.53 ± 0.05, 0.32 ± 0.14, le 0.30 ± 0.09, ka ho latellana, ho 48 h ka mor'a ente (P < 0.05). Ho thibela lithuto tse nang le 64Cu-L19K-FDNB boteng ba peptide e feteletseng e sa ngolisoang e bontšitse 53% ho fokotseha hoa hlahala ka 48 h ka mor'a ente. Qetello: Thutong ena ea bopaki ba maikutlo, Tšebeliso ea li-peptide ligand e tlamang e tlamang khahlanong le VEGF e ntlafatsa ho bokellana ha tracer sebakeng sa tumor ka vivo., ha e bapisoa le li-analogue tsa eona tsa peptide tse tlamang tse sa sebetseng. Mokhoa ona ke sesebelisoa se ts'episang ho matlafatsa matla a li-peptide probes joalo ka li-aging agents.
Litšebeletso tse Amanang tsa Phetoho ea Peptide
glycosylation ea peptide
glycosylation ea peptide
Peptide glycosylation ke phetoho e kopanetsoeng e ka ntlafatsang thepa ea physicochemical ea peptide.
Bala haholoanyanePhosphorylation ea peptide
Phosphorylation ea peptide
Phosphoralation e ka hlaha ka Serine (S, Ho ba), Threonine (T, Thr) le Tyrosine (Y, Tyr) liketane tse mahlakoreng ka ho theha bond ea phosphoester
Bala haholoanyaneLi-peptide tse tloaelehileng
Li-peptide tse tloaelehileng
Kenyelletso ea li-amino acid tse peli tseo e seng tsa tlhaho tse nang le α-methyl, lihlopha tsa α-alkenyl nakong ea motsoako o tiileng oa liketane tsa peptide.
Bala haholoanyanePeptide ea cyclic
Peptide ea cyclic
Peptide cyclization e ntlafatsa botsitso ba li-peptide (e amanang le li-analogue tsa bona tsa mela) 'me ke leano le tloaelehileng ho nts'etsopele ea peptide.
Bala haholoanyanephetoho ea peptide
Boiphihlelo bo pharalletseng ba phetoho ea peptide, ho fana ka mekhoa e mengata e sebetsang ea lipatlisiso tsa peptide.
