Mgbanwe Peptide
Peptides nwere stapled
Kedu ihe bụ Stapled Peptides?
Nnyocha egosiwo na peptides nwere usoro α-helical na ọgaranya na ụgwọ dị mma nwere ike ịgafe akpụkpọ anụ. Agbanyeghị, otu oge kewapụrụ na ahụ nne na nna, peptide enweghị ike idobe usoro nke abụọ mbụ ya, na conformational akwusighi ike na-eduga na ike ọgwụgwụ nke njikọ ya na protein, ebe peptides linear nkịtị enweghị ike ịgafe akpụkpọ ahụ cell ma na-agbaze ya ngwa ngwa. Mgbe mgbalị na-aga n'ihu, Verdine et al. mepụtara usoro ọhụrụ nke peptide, A na-akpọ peptide a stapled peptide, ọ bụ ihe niile na-carbon scaffold nwere α-helical Ọdịdị, All-carbon scaffold na-eme ka usoro α-helical guzosie ike, nke na-ewusi mmekọrịta dị n'etiti ụmụ irighiri peptide na protein, na peptide stapled nwere ike ịgafe akpụkpọ ahụ cell na ọ dịghị mfe ịbụ hydrolysed, nke nwere ọrụ nkà mmụta ọgwụ dị elu ma e jiri ya tụnyere ọgwụ ndị dị nta nke mbụ na ọgwụ ndị dabeere na protein. ọrụ ọgwụ dị elu karịa obere ọgwụ molekul gara aga na ọgwụ protein.
Sayensị Peptides na-emepe emepe
Ọdịiche dị n'etiti njikọ nke peptide stapled na njikọ peptide nkịtị bụ iwebata amino acid abụọ na-abụghị eke nwere otu α-methyl na α-alkenyl n'oge njikọ siri ike nke agbụ peptide., na mgbe ahụ, mmeghachi omume nbibi nke mgbagwoju anya olefinic na-apụta n'etiti amino acid abụọ na-abụghị nke okike iji mee ka ọkpụkpụ carbon niile nwere nhazi α-helical kwụsiri ike., wee mepụta peptide stapled.
Chemistry peptide stapled
Ọgbọ nke mbụ Grubbs katalite (aka ekpe) na tricyclohexylphosphine (PCy3) ligands na apical positioned carbene carbon bụ ruthenium siri ike siri ike ejiri mee ihe maka metathesis olefin na peptides.. Nnyocha ndị sochirinụ dugara n'ichepụta ihe nrụpụta ọgbọ nke abụọ Grubbs kwụsiri ike karịa (etiti). Ọgbọ nke atọ na-akpata, nke a makwaara dị ka Hoveyda-Grubbs catalyst (nri), na-anọchi N-heterocyclic carbene ligand maka benzylidene ligands nke nwere chelating ortho-isopropoxy otu jikọtara na benzene mgbanaka..
Otu mmeghachi omume peptide stapled
Otu mmeghachi omume peptide stapled. Ntinye nke alfa-4-n-pentenylalanine abụọ (S5) mwepu n'ime eriri peptide na-eme ka mgbanaka mechie metathesis (ya bụ., Grubs mmeghachi omume) iji mepụta otu peptide stapled. Mgbe n = 3 (ya bụ. ya na 3 amino acid dị n'etiti ihe fọdụrụ S5) A na-ama ụdị isi ihe dị ka i, i + 4.
Otu Nhazi Staple
Ọrụ dị elu na ọnọdụ dị nro nke mmeghachi omume "pịa". (Ọla kọpa-catalyzed Huisgen 1,3-dipolar cycloaddition mmeghachi omume) jikọtara ya na ịdị mfe nke njikọ nke amino asịd na-ekwekọghị n'okike, na-enye ohere maka njikọ dị mfe nke peptides triazole-stapled. Ọmụmaatụ, ngwakọta nke L- Nwere ike (εN3) na D-Pra (D-propargylalanine) Enwere ike iji dochie anya na ọnọdụ i na i+4 maka ọgbọ nke peptides nke triazole stapled..
Ntụtu aka egosipụtara
Iwu imewe maka peptides stapled nwere ọrụ in vivo yana ngwa ha na ndị na-emegide Mdm2/X.
Ọ bụ ezie na stapled α-helical peptides nwere ike dozie ebumnuche ndị siri ike, Nghọta na-adịghị mma na-egbochi ọganihu ha maka ime ka mkpụrụ ndụ na-agafe agafe ebe ha na-ezere nsí ndị na-enweghị isi.. Site synthesizing >350 ụmụ irighiri ihe, anyị na-ewepụta usoro ọrụ maka ịchọpụta peptides stapled megide Mdm2(X) nwere ọrụ in vivo na enweghị mmetụta na-apụ apụ. Nghọta ndị bụ isi gụnyere njikọ doro anya n'etiti lipophilicity na permeability, mwepụ nke ezigbo ụgwọ iji zere nsí ndị ezubere iche, ntunye ihe fọdụrụ nke anionic iji kwalite solubility/omume, njikarịcha ogologo C-terminal / ike iji kwalite ike, na njikarịcha ụdị staple/nọmba iji zere polypharmacology. Ngwa na-arụ ọrụ na-enye peptides na >292x emelitere ikike mgbasawanye cell yana enweghị mmetụta mgbasa cell na-apụ apụ ( > 3800x ntụzịaka nke ebumnuche). Itinye 'iwu imewe' ndị a na Mdm2 dị iche(X) usoro peptide na-akawanye mma ( > 150x) ike cellular ma na-ewepụ nsí ndị ezubere iche. Usoro ọrụ akọwapụtara kwesịrị ịkwado mmetụta ọgwụgwọ, ọkachasị maka ebumnuche ndị ahụ dịka Mdm2(X) ndị nwere oghere hydrophobic ma bụrụ ndị a na-atụ anya ya na motif helical.
Ọrụ mgbanwe Peptide emetụtara
peptide glycosylation
peptide glycosylation
Peptide glycosylation bụ mgbanwe covalent nke nwere ike melite njirimara physicochemical nke peptides.
GỤKWUOpeptide phosphorylation
peptide phosphorylation
Phosphoralation nwere ike ime na Serine (S, Ịbụ), Threonine (T, Thr) na Tyrosine (Y, Taịa) ụdọ akụkụ site n'ichepụta njikọ phosphoester
GỤKWUOPeptides nwere stapled
Peptides nwere stapled
Mmalite nke amino acid abụọ na-ekwekọghị n'okike nwere α-methyl, Otu α-alkenyl n'oge njikọ siri ike nke agbụ peptide.
GỤKWUOPeptide cyclic
Peptide cyclic
Peptide cyclisation na-akwalite nkwụsi ike nke peptides (ikwu na ha linear analogues) na bụ atụmatụ a na-ahụkarị na mmepe peptide.
GỤKWUOmgbanwe peptide
Ahụmahụ sara mbara na mgbanwe peptide, na-enye ọtụtụ ụzọ dị mma maka nyocha peptide.
