Chemistry Radikal dị nro maka Mgbanwe Peptide n'oge

Ihe “Milder” Pụtara n'ezie n'okwu a

Dị nwayọọ, na peptide chemistry, abụghị okwu ire ahịa. Ọ na-egosipụta paramita arụ ọrụ kpọmkwem: pH 6-8, okpomọkụ ≤ 37 Celsius C, aqueous-dakọtara ihe mgbaze, na ndidi maka hydroxyl, carboxyl, amino, ọzọ, imidazole, na agbụ akụkụ guanidinium na-enweghị ihe nchebe. Usoro ebipụtara maka ndakọrịta bioconjugation na-akọwapụta oke nke a n'ụzọ doro anya, na akwụkwọ kemịkalụ radical na nso nso a na-akọpụta nnwale ndị emere kpọmkwem n'ime ya.

Nke ahụ kwuru, "dị nwayọọ" ka na-adịgasị iche n'ofe klaasị mgbanwe akọwara n'okpuru. Ụzọ Photoredox na-eji organic photocatalysts na-acha anụnụ anụnụ ma ọ bụ akwụkwọ ndụ akwụkwọ ndụ LED na-abụkarị ndị kacha dakọtara na ndabara.. Ụzọ kascade dabere na okpu na ụzọ njikọ C-H/S–H electrochemical nwere ike ịchọ ihe mgbaze. (na-emekarị DMSO/ ngwakọta mmiri) na oke nke na-emetụta solubility nke ogologo oge ma ọ bụ karịa nchịkọta-enwere ike usoro. eduzi C(sp³)-Hzọ arylation H - ọkachasị palladium-catalyzed variants - na-etinye ihe mgbochi ndị ọzọ na-eduzi ntinye na mwepụ otu., nke na-agbakwunye nzọụkwụ na isi mmalite adịghị ọcha. Ajụjụ maka otu mmepe ọ bụla abụghị ma usoro ọ dị "dị nwayọọ n'ụkpụrụ" mana ma ọ dị nro zuru oke maka usoro a kapịrị ọnụ yana ngwa mgbada..

Njikọ Photoredox: Ihe Ihe akaebe Na-akwado

Photoredox catalysis ewepụtala akụkụ kachasị ukwuu na nke enwere ike imepụtaghachi nke data arụmọrụ peptide n'oge ikpeazụ.. The isi usoro - na-akpali akpali a photocatalyst na anya ìhè, na-amụba intermediates reactive radical na akọwapụtara ọnọdụ, na ijikọ ha na ndị na-anabata ma ọ bụ ndị mmekọ - na-enye chemoselectivity site na eletrọnịkị selectivity nke steeti nwere obi ụtọ karịa site na ichekwa-otu ụzọ..

Tryptophan dị ka aka mbụ. C2-alkylation na C2-sulfenylation nke peptides nwere tryptophan ka egosipụtara n'okpuru ọnọdụ enweghị igwe na enweghị fotocatalyst., Nke ikpeazụ na-eji arylthiathrenium salts. A 2023 akuko na Akwụkwọ ozi Organic (ACS, chemoselective n'oge na-arụ ọrụ site na photocatalytic C2-alkylation nke tryptophan.) Akọwapụtara nnabata otu na-arụ ọrụ dakọtara na aspartate na-enweghị nchebe, glutamate, lysine, na serine n'akụkụ ụdọ - nke bụ opekempe mmanya maka credible peptide n'oge ikpeazụ-ogbo functionalization. A 2024 Mgbanwe tryptophan clickable kọwara na Ọganihu Sayensị akọwara na-enweghị ihe mkpali, Oge ngwụcha nke C2-sulfenylation na-anabata ihe fọdụrụ cysteine ​​n'efu, ule na-achọsi ike nke chemoselectivity.

Histidine alkylation. Ụdị minisci-ụdị C-H nke na-ahụ anya nke peptides nwere histidine na-eji 4-alkyl-1,4-dihydropyridines dị ka radical precursors ka akọpụtala.. Histidine bụ ihe fọdụrụnụ na-enwe nsogbu na ọnọdụ fotochemical n'ihi ike oxidation ya., Ya mere, ụzọ akwadoro nke ezubere iche maka ọnọdụ imidazole C2 ma ọ bụ C5 na-agbakwunye aka dị iche iche nke kemịkal.

Dehydroalanine (Da) dị ka a vasatail radical receiver. Dha arụnyere enzymatically ma ọ bụ site na ntụgharị kemịkalụ sitere na serine ma ọ bụ cysteine ​​na-eme dị ka onye na-anabata ụdị Michael dị n'okpuru ọnọdụ dịgasị iche iche.. A 2025 akụkọ na Nrụpụta saịtị nke glycopeptides jikọtara ya site na fotoredox catalysis (PubMed) eji Dha dị ka onye na-anabata N-glycosyl oxamic acid radicals n'okpuru ìhè a na-ahụ anya, na-egosipụta mgbakwunye ụdị Giese na-enweghị ichebe glycine fọdụrụnụ, alanine, ma ọ bụ serine residues dị. Ọnụ ọgụgụ mkpụrụ na diastereoselectivity dị na ọmụmụ ihe ahụ - yana enweghị ngwọta stereoselective maka mgbakwunye Dha na ọtụtụ akụkọ mbụ - na-egosipụta ọdịiche na-adịgide adịgide.: radical mgbakwunye na Dha na-adịkarịghị stereoretenti, nke dị mkpa mgbe nhazi α-carbon na-emetụta njikọ nnabata ma ọ bụ nkwụsi ike protease.

Njikọ Decarboxylative. Ndị otu MacMillan gosipụtara na C-terminal carboxylate nke peptides nwere ike ịhọrọ oxidized yana jikọta ya site na radical decarboxylation n'okpuru ìhè anụnụ anụnụ., na-erigbu ihe dị iche na oxidation ike n'etiti esịtidem na ọnụ carboxylates. Ụzọ a dị ọcha n'usoro ihe eji arụ ọrụ ma na-ezere mgbochi n'akụkụ ọ bụla, mana ọ na-eri C-terminus - nke na-amachibido itinye ya n'ọrụ ọ gwụla ma enwere C-terminus efu ma ọ bụ ihe mgbaru ọsọ bụ akara akara..

ndetu mmepe: Usoro Photoredox egosila nnabata otu kachasị arụ ọrụ n'ofe akwụkwọ. Ajụjụ mepere emepe maka ojiji mmepe bụ reagent na mwepụ fotocatalyst, mmetụta oxygen n'oge mmeghachi omume na ọrụ, na ma ihe mgbaze usoro (Ọtụtụ mgbe DMSO/mmiri) dakọtara na nchacha ala na lyophilization na-enweghị iwebata ihe fọdụrụ na-adịgide adịgide.

Okpu na MHAT: Nkwalite n'ime ime na-enweghị ọrụ mbụ

Hydrogen atom nyefe (Okpu) kemistri nwere niche dị iche na fotoredox. Kama ilekwasị anya n'aka aka na-arụ ọrụ redox, Ụzọ dabere na okpu na-ewepụ atom hydrogen sitere na C(sp³)-H agbụ iji mepụta radicals dabere na carbon n'ọnọdụ ga-achọ ka ndị otu na-eduzi ma ọ bụ prefunctionalization.. N'ọnọdụ nke mgbanwe peptide, nke a pụtara ihe abụọ n'ụzọ bụ isi: arụ ọrụ dịpụrụ adịpụ site na usoro ịgbagharị 1,5-HAT yana mmeghachi omume cascade nke na-ejikọta ọgbọ na-egbuke egbuke na nzọụkwụ nke abụọ na-eme njikọ catalytic..

Peptide Synthesis A 2025 akwụkwọ n'ime Ọganihu Chemistry Organic (RSC, alkylation nke akụkụ atọ nke glycine na-emepụta na peptides site na saịtị-ahọrọ 1,5-HAT cascade) egosipụtara na-ahụ anya-ìhè-mgbasa ozi N-etiti radical ọgbọ sochiri 1,5-hydrogen atom nyefe na α-carbon nke glycine residues., na-enyere alkylation akụkụ atọ. Nhọrọ a na-esite na geometry nke 1,5-shift kama site na mmasị eletrọnịkị maka yinye akụkụ ọ bụla., nke nwere ma uru na njedebe: Usoro a na-emetụta n'ụzọ sara mbara na usoro nwere glycine mana ọ naghị amata ọdịiche dị n'etiti ihe fọdụrụ n'otu ebe ahụ n'agbụ ogologo..

Okpu enyemaka igwe, mgbe ụfọdụ a na-ezo aka na cobalt ya- ma ọ bụ ụdị mgbasa ozi ígwè dị ka MHAT, na-eweta njikwa ọzọ. Igwe hydride metal na-emepụta carbon radical n'okpuru ọnọdụ dị nro - na-abụkarị okpomọkụ ụlọ, hydrogen ma ọ bụ silane dị ka isi iyi hydrogen - na ihe na-akpata radical nwere ike ọnyà site na alkene ma ọ bụ onye na-anabata radical n'otu flask.. Maka ngwa peptide, ajụjụ dị mkpa bụ ma ihe na-emepụta ígwè na hydrogen-source reagent kwekọrọ na histidine, methionine, na agbụ akụkụ cysteine, ihe niile bụ ndị mmekọ mmeghachi omume nwere ike ịsọ mpi. Usoro mmalite ebipụtara dị maka ihe dị mfe dipeptide na trieptide substrates; nkwado n'ogologo ogologo ogologo ogologo nwere ọtụtụ eriri akụkụ reactive na-anọgide na-ejedebe na akwụkwọ ndị mbụ dị ka etiti 2026.

ndetu mmepe: Ụzọ okpu na MHAT na-adọrọ mmasị maka ịmegharị usoro ebe ejiri aka na-egbuke egbuke (Cys, Tp, Da) anọghị ya ma ọ bụ ga-echekwa ya maka ọrụ ndu. Ihe ịma aka nke nhọrọ saịtị ahụ bụ ezigbo yana dabere n'usoro - peptide dị mkpụmkpụ ebe selectivity mara mma nwere ike ịkpa àgwà dị iche iche na usoro 20 fọdụrụnụ nwere ọtụtụ ọnọdụ enweghị ike ịsọ mpi..

C(sp³)–H arụ ọrụ: Ndozi azụ-n'akụkụ

eduzi C(sp³)–H arụ ọrụ na-anọchite anya ogwe aka kacha nwee olile anya nke kemistri a maka ngwa peptide, na-ezubere iche n'ime ọkpụkpụ azụ-n'akụkụ ọnọdụ na-enweghị omenala reactive aka. Ụzọ abụọ egosipụtara ike nkwadebe-ọnụ ọgụgụ na mkpụrụ peptide.

arylation na-eduzi agbụ akụkụ. A 2024 ọmụmụ sitere na Hou et al. - chịkọtara na a 2026 Nyocha RSC (Ọganihu na nso nso a na mgbanwe saịtị nke peptides na protein) - akọwara β-C(sp³)-H arylation nke ọnọdụ dị n'ime na peptides linear na cyclic na-eji S-alkyl cysteine ​​dị ka ndị na-eduzi na 2-pyridone dị ka ligand inyeaka., n'okpuru palladium catalysis. Usoro a nwetara arylation na β-carbon nke ihe fọdụrụ n'akụkụ otu ntụzịaka nke cysteine ​​nwetara n'okpuru ọnọdụ dị nro dị oke egwu maka ịgbalite C-H palladium-catalyzed..

Otu ndị na-eduzi agbakwunyere ọkpụkpụ azụ. A 2025 akuko na JACKS (PubMed, Pd(II)-catalyzed C(sp³)–H functionalization na-eduzi nke mbughari, amidoxime ether a na-etinye n'azụ) kọwara ntinye amidoxime ether na njikọ amide ọ bụla na ọkpụkpụ azụ, iji ya dị ka otu ntụzi aka mbughari maka C na-esote(sp³)-H arylation. A na-etinye amidoxime ether ma wepụ ya na usoro sịntetịt dị iche iche, na-agbakwụnye mgbanwe abụọ na ụzọ ahụ - mana mgbanwe ọnọdụ ọ na-enye enweghị ihe ọ bụla na usoro mgbanwe ọkọlọtọ ugbu a..

Maka usoro-agnostic n'ọkwa, klaasị a nwere mmetụta kemịkal. The bara uru ibu - palladium mwepụ, eduzi otu ntinye na mwepụ, SPPS - ndakọrịta otu nchekwa dakọtara, na enwere ike imeghari na α-carbon n'okpuru palladium catalysis - bụkwa nke kachasị njọ n'ime ezinụlọ mgbanwe atọ a tụlere ebe a..

Ụzọ Radikal dabere na sọlfọ: Chemoselectivity Data kwadoro

Cysteine ​​​​ka bụ ihe fọdụrụ na nyocha nke saịtị maka mgbanwe peptide na-ahọrọ saịtị n'ihi na sọlfọ nucleophilicity ya na redox kemịkalụ dị iche na ụdọ akụkụ ndị ọzọ iji kwe ka mmeghachi omume dị ọcha site na isi mmalite radical electrophilic kwesịrị ekwesị.. Ọtụtụ akụkọ 2024-2025 na-agbatị ngwa ngwa a na ntụzịaka dabara na mmemme njikọ..

Aryl radicals sitere na aryl pinacol boronates n'okpuru ọnọdụ mmiri dị nro ka egosipụtara iji mee nhọrọ S-arylation nke peptides na protein. (aryl radicals sitere na aryl pinacol boronates maka peptide na mgbanwe protein, TU Darmstadt/Wiley). Nhọrọ maka sọlfọ n'elu ụdọ akụkụ amino acid aromatic n'okpuru aqueous, ọnọdụ adịghị anọpụ iche na-anọchite anya ọganihu bara uru gbasara kemịkalụ nnu aryl diazonium, nke dị nnọọ obere nhọrọ.

Ụzọ eletrọnịkị nke C-H/S-H cross-coupling maka peptides nwere cysteine., gụnyere macrocyclization intramolecular, a kọwara na Nkwukọrịta okike (C-H/S-H na-eme ka electro-induced maka ịrụ ọrụ / macrocyclization nke cysteine ​​nwere peptides., 2025). Atụmatụ umpolung - na-emepụta thiyl radical electrochemically na ijikọ ya na njikọ C-H dị n'akụkụ - na-arụ ọrụ na-enweghị oxidant mpụga ma ọ bụ photocatalyst ma na-anabata ọtụtụ ụdọ akụkụ..

Maka mmemme metụtara stapled peptides, Njikọ dị ka ADC, ma ọ bụ akara fluorescence na ọnọdụ akọwapụtara, Ụzọ nhọrọ sọlfọ ndị a na-anọchi anya ebe ntinye ihe ize ndụ kachasị dị ala n'ihi na data chemoselectivity dị n'ogologo ogologo ogologo ogologo ogologo ogologo na gburugburu mpaghara mpaghara dị iche iche..

Ndakọrịta, adịghị ọcha, na ajụjụ nyocha nke a na-aghaghị ịza

Kemistri akọwara n'elu dị adị ma nwee ike imepụtagharị n'ọtụtụ nchọta. Ntụgharị asụsụ gaa na ọkwa nkwadobe na mmepe chọrọ azịza ziri ezi nye ụdị ajụjụ anọ tupu ụzọ ọ bụla n'ime ụzọ ndị a abanye n'usoro mmepe..

Ntụle ndakọrịta

Tupu itinye aka n'ụzọ mgbanwe radical nke oge ikpeazụ, otu mmepe kwesịrị ịsepụta ihe ndị a:

Amụma profaịlụ adịghị ọcha

Mgbanwe mgbanwe nke oge ikpeazụ na-ewebata otu ụdị adịghị ọcha dị iche na adịghị ọcha ndị SPPS nwetara.. Na-atụ anya na hazie usoro nyocha maka:

• Ihe mmalite anaghị emeghachi omume: peptide na-enweghị njikọ na-ejikọta ma ọ bụ nso ngwaahịa ahụ

• Ụdị agbanweela karịa: ọ bụrụ na ihe karịrị otu saịtị reactive dị (eg., abụọ tryptophan residues), ọtụtụ ngwaahịa mgbanwe ga-apụta dị ka akara ngosi dị elu na ESI-MS ma ọ bụ MALDI-TOF

• Ngwaahịa Regioisomeric: maka mgbakwunye Dha radical ma ọ bụ histidine alkylation, Isomers ọnọdụ dị iche na saịtị nke njikọ nwere ike ịbụ nke RP-HPLC naanị enweghị ike ịmata ya.

• Ngwaahịa oxidation: Ọnọdụ radical nwere ike oxidize methionine na sulfoxide ma ọ bụ tryptophan na oxindole - ọnụ ọgụgụ kasị elu nke dị nso na mmalite ihe na chromatography na-agbanwe agbanwe.

• Ntugharị ewepụtara nke katalyst: organic photocatalyst iberibe, ihe ndị dị na palladium (maka ịrụ ọrụ C-H), ma ọ bụ ngwaahịa reagent sitere na ngalaba-reagents HAT nke na-etolite adducts na peptide

Usoro iwu na mmetụta CMC nke ala adịghị ọcha a dabara na EMA Ntuziaka na mmepe na nrụpụta nke Peptides sịntetik, nke na-akọwa n'ụzọ doro anya usoro reagents, elemental adịghị ọcha, na usoro njikwa maka ndị intermediates sịntetik.

Ihe nyocha chọrọ

Ọkọlọtọ RP-HPLC na 214 nm, nke na-arụ ọrụ nke ọma maka ịkọwapụta adịghị ọcha nke SPPS, ezughị oke maka mpụta mgbanwe mgbanwe oge ogbo. Ndị otu kwesịrị ịhazi maka:

• LC-MS ma ọ bụ LC-HRMS dị ka ngwa njirimara bụ isi - achọrọ MS ka ịmata ọdịiche dị n'ihe mmalite na-ejikọtaghị na ngwaahịa mono-modified mgbe ha nwere njide chromatographic yiri ya.

• Ụdị chromatography nke orthogonal (eg., HILIC ma ọ bụ IEX na mgbakwunye na RP) Mgbe a na-atụ anya regioisomers; regioisomers nwere otu uka agaghị ekpebi site na nchọpụta oke naanị

• Amino acid analysis (AAA) maka ikwado na ihe mejupụtara amino acid mgbe emezigharịrị dabara na otu mmemme mgbakwunye, ọ bụghị mgbawa ọkpụkpụ azụ ma ọ bụ mfu agbụ akụkụ pụrụ iche

• Ụzọ nkwụsi ike-egosi nke nwere ike ịmata ọdịiche nke synthesis adịghị (dị na mbụ ogbe) ngwaahịa na-emebi emebi nke na-apụta ka oge na-aga - dị oke egwu mgbe usoro mgbanwe mgbanwe na-ewebata chromophores ọhụrụ ma ọ bụ otu ọrụ na-agbanwe profaịlụ oxidation ma ọ bụ hydrolysis kwụsie ike nke peptide.

Injinia Ọnụ Ọgụgụ

Ụzọ Photoredox na-eweta ihe ịma aka n'ịkọwapụta n'ụzọ nkà na ụzụ n'ihi na nnyefe foton anaghị adabere n'ahịrị. Ọkụ ọkụ ahụ merenụ dị n'etiti flask 1-liter bụ ntakịrị nke ahụ dị n'elu arịa ahụ., na geometry oriọna-na-reactor na-ekpebi ntughari n'ụzọ na-enweghị analogue na kemịkalụ na-ekpo ọkụ.. Ndị na-ahụ maka kemịkalụ na-efe efe emebere maka photocatalysis na-elebara nke a anya site na ihe nkiri dị mkpa ma ọ bụ site na irradiation., na ọtụtụ atụmatụ reactor akwadoro ugbu a dị maka mmepe usoro ọgwụ - mana ha chọrọ isi ego n'ihu yana nkwalite usoro n'usoro ọkwa ọ bụla..

Ụzọ okpu na electrochemical nwere profaịlụ nrịgo elu dị iche iche. Ebe elu electrode na-ebu amụma karịa nnyefe foton, ma electrochemical ụzọ ewebata ajụjụ banyere electrode ihe ndakọrịta, mwepụ electrolyte, na njupụta ugbu a uniformity na nkwadebe ọnụ ọgụgụ.

Maka klaasị mgbanwe niile, Ntugharị site na nchacha HPLC nke nyocha gaa na HPLC nkwadebe na-ewebata ihe ịma aka mkpebi ndị ọzọ. Ngwa ime mgbanwe n'oge na-adịghị anya yana regioisomers mono-modified na ọnụ ọgụgụ nyocha ga-achọ iji nlezianya emegharịghachi nke mkpọda gradient., mobile agba mejupụtara, na kọlụm kemịkalụ na preparative loading - na preparative HPLC mgbake site na mgbagwoju ngwakọta bụ ọnụego-mmachi nzọụkwụ na peptide ọnụ ọgụgụ-elu ugboro ugboro karịa njikọ n'onwe ya..

A Framework maka Nyochaa ekwe omume nkuchi

Kama ịnakwere nke ọ bụla n'ime usoro ndị a n'ùkwù, Ndị otu mmepe kwesịrị ịme ntule ike haziri ahazi jikọtara na ebumnuche mgbanwe a kapịrị ọnụ. Matriks mkpebi a na-egosipụta ndakọrịta na akụkụ ihe egwu ndị a tụlere n'elu.

Ịgafe ndepụta ndenye n'uju anaghị ekwe nkwa ịga nke ọma - mana ọ na-achọpụta nnwale ndị ị ga-ebute ụzọ tupu ịme akụrụngwa mmepe.. Ihuenyo ndakọrịta dara ada na nha 5-milligram na-echekwa ogologo oge karịa otu ọdịda ahụ 100 milligrams n'oge mbubreyo CRO.

Ebe Ngwakọta Ngwakọta dị adị nwere ike inye aka

Mmemme na-enyocha ụzọ ọhụrụ ndị a n'akụkụ ndị dị adị, Usoro ngbanwe dabara adaba ga-ezo aka n'ihe ndị otu ha nwere ike ime na-enweghị usoro mmepe omenala. nyiwe mgbanwe peptide nke na-ejikarị aka aka kemịkalụ (azides, na chess, alkynes), ntinye nke glycopeptide, na fluorescent ma ọ bụ isotope label conjugation Ọ na-arụkwa ọrụ n'ime envelopu nnabata nke otu na-arụ ọrụ nke na-eme ka usoro oge ikpeazụ na-arụ ọrụ ịgbasa.

Uru nke ụzọ ndị ọhụrụ radical abụghị iji dochie ụzọ njikọ njikọ ndị a siri ike - ọ bụ ịnweta ọnọdụ mgbanwe nke kemịkalụ oge gboo enweghị ike iru., karịsịa n'ime ime ọkpụkpụ ọnọdụ na residues na-enweghị adaba nucleophilic aka. Mgbe ikike ahụ bụ ihe mgbochi, Usoro arụ ọrụ radical ezubere iche kwesịrị ka etinyere nyocha na usoro mmepe ego.

Maka ihe ọ bụla ọzọ, guzosie ike omenala peptide njikọ usoro nrụ ọrụ nwere njirisi nnabata adịghị ọcha akọwapụtara yana ngwugwu nyocha akwadoro ka bụ ụzọ ngwa ngwa gaa na ewepụtara QC., mmepe-njikere ogbe.

Ajụjụ Ndị A Na-azabeghị

Iji ezigbo ngwa ahịa mechie: Akwụkwọ 2024-2025 egosila na kemistri dị nro na-arụ ọrụ na peptides n'okpuru ọnọdụ nchọpụta.. O guzobebeghị, maka ọtụtụ ụzọ:

1. scalability: ka ntughari na selectivity si eme na 100 milligrams megide 1 gram megide 100 gram n'okpuru usoro-ọnọdụ ezi uche, na mwepu oxygen kwesịrị ekwesị na njikwa okpomọkụ

2. Stereoselectivity na Dha: mgbakwunye radical na dehydroalanine na-ewepụta etiti α ọhụrụ nwere oke diastereomeric na-agbanwe.; nke a bụ nsogbu mepere emepe, na nso nso a ChemBioChem nyochaa (Ọganihu na mgbanwe dehydroalanine kpọmkwem, 2025) gosipụtara ya n'ụzọ doro anya ka edozibeghị maka ọtụtụ klaasị mkpụrụ

3. Usoro usoro iwu: Ọ dịghị nke ọ bụla n'ime ụzọ ndị a nwere, ka ọha mmadụ mara, bụrụ isiokwu nke ngalaba CMC IND na-ekpuchi ntozu adịghị ọcha, Nyocha adịghị ọcha genotoxic nke ihe fọdụrụ na fotocatalyst, ma ọ bụ nkwụsi ike na-egosi usoro nkwado maka API radical-modified - a ka ga-atọkwa ntọala ntọala.

4. Nkwụsi ike ogologo oge nke njikọ mgbanwe: mgbakwunye radical na Dha, Tp, na Ya kee C–C, C–S, ma ọ bụ njikọ C-N nwere profaịlụ nkwụsi ike dị iche iche; data ọmụmụ kwụsie ike dị obere maka ọtụtụ conjugates

Ihe ndị a abụghị ihe kpatara ịchụpụ kemịkalụ. Ha bụ usoro nnwale na usoro iwu nke a ga-emerịrị yana mkpebi ọ bụla iji tinye usoro ndị a n'ime usoro mmepe ụlọ ọgwụ..

Nzọụkwụ ọzọ bara uru maka otu mmepe

Maka otu ndị na-arụsi ọrụ ike na-enyocha ma ịrụ ọrụ nke obere oge dị n'ime atụmatụ mgbanwe ha, omume kacha arụpụta nso nso bụ:

• Mepụta obere ihe ga-ekwe omume (5-10 mg) na kpọmkwem usoro, na-ezubere iche ụdị nke fọdụrụ kpọmkwem, n'okpuru ọnọdụ radical tụrụ aro - na njirimara LC-HRMS nke ngwakọta crude, ọ bụghị naanị HPLC ịdị ọcha

• Rịọ data nkwụsi ike na njikọ radical adduct n'okpuru oke pH, nrụgide oxidative, na nrụgide okpomọkụ tupu ịmepụta usoro nchacha

• Map profaịlụ adịghị ọcha nke crude megide ihe usoro HPLC gị nwere ike idozi, na-eji ụkpụrụ ntụnyere spiked ma ọ bụrụ na ọ dị

• Chọpụta ma usoro iwu maka klaasị ma ọ bụ reagent dị na nchịkọta IND CMC ebipụtara., Akwụkwọ ntuziaka FDA, ma ọ bụ akụkọ nyocha EMA

Chemistry na-aga ngwa ngwa. Akụrụngwa mmepe nke nyocha na usoro iji ya mee ihe n'ụzọ kwesịrị ekwesị na mmemme mmepe na-ewe ogologo oge iji wuo ya. Bido ihe owuwu ahụ ugbu a, na usoro ebumnuche akọwapụtara nke ọma, bụ ụzọ ziri ezi.

MOL mgbanwe na-akwado ndị otu mmepe na-agagharị chọrọ mgbanwe mgbagwoju anya karịa karịa 300 ụdị mgbanwe otu ọrụ, gụnyere njikọ kemịkalụ pịa, njikọ nke glycopeptide, na mmepụta peptide nke akpọrọ isootope n'ime klaasị 100 gburugburu n'ichepụta ihe. Ọ bụrụ na mmemme gị gụnyere ọnọdụ mgbanwe ma ọ bụ ebumnuche njikọ nke dabara na usoro SPPS ọkọlọtọ, mkparita uka n'ihe gbasara nka bu isi mmalite bara uru.