Ihuenyo Peptide Mgbakọ: Ihe mbụ synthesis
Nlele nyocha nke ọma dị elu, generative AI, simulations molecular dynamics agbanweela n'ụzọ doro anya nchọpụta peptide n'oge mbụ. Usoro mgbakọ na mwepụ ọgbara ọhụrụ nwere ike nyochaa ọtụtụ nde usoro ndoro-ndoro anya n'ime awa, na-ebute ụzọ hits dabere na ijikọ ike efu (D G kechie), interfacial kọntaktị njupụta, na nhọrọ nhọrọ ebumnuche buru amụma. Agbanyeghị, Ndị otu nyocha biopharmaceutical na-enwekarị nkụda mmụọ mgbe ha na-agbanwe site na nsonaazụ silico gaa na nkwado ụlọ nyocha mmiri.: kacha-ọkwa mebere hits na-esikarị ike synthesize, sachaa, ma ọ bụ igbari na isi bioassays.
Peptide emebere nke ọma nke na-enweta akara n'elu 0.1% Ihuenyo mebere nwere ike daa ngwa ngwa n'oge njikọ peptide siri ike (SPSS) n'ihi nchikota n'okirikiri n'okirikiri, na-asọba n'ime gel na-adịghị ike n'oge trifluoroacetic acid (TFA) ikpochapu, ma ọ bụ mepụta mgbakọ colloidal nke na-emepụta akara adịgboroja na nyocha nyocha. Idozi esemokwu a chọrọ ịgafe n'ihu nchọpụta nsogbu. Biopharma R&Ndị otu D ga-enwerịrị ihe agbakwunyere peptide kụrụ triage ọrụ nke na-enyocha ụgwọ njikọ nyocha peptide mgbakọ na mwepụ tupu nyefee usoro na resin synthesizer.
Site n'inyocha "Peptide VB" - onye nnọchi anya 22-mer computational hit onye ndoro-ndoro ochichi mebere iji gbado anya mmekọrịta protein-protein. (PPI) interface — isiokwu a na-akọwapụta usoro mkpebi ebutere ụzọ. Anyị na-enyocha otu esi akọwa ụkpụrụ kọntaktị kọntaktị, Maapụ buru amụma ibu anụ ahụ dị ka patches hydrophobic na ihe egwu mkpokọta, ma tụgharịa amụma ndị ahụ n'ime mkpebi njikọ kemịkal siri ike-gụnyere mkpado solubilizing, hydrocarbon stapling, na akara saịtị akọwapụtara-iji wepụta ngwa nyocha ngwa ngwa yana iji obere nnwale..
Banyere Onye dere ya:
Dr. Aris Vance, Ph.D. | Onye isi ọrụ sayensị & Onye isi Peptide Chemistry na MOL Changes
Dr. Vance na-abịa 18 afọ nke ahụmahụ n'ichepụta ọgwụ ezi uche dị na ya, njikọ peptide siri ike (SPSS), na mgbako hit triage. Ọ na-eduzi otu nyocha na mmepe na MOL Changes, chịkọta amụma mmụta igwe na njikọ kemịkalụ omenala na klaasị 100 mmepụta ihe adịghị mma.
Mgbakọ kụrụ Triage: Idozi ụkpụrụ kọntaktị ihu & Usoro nhazi
Mgbe ọba akwụkwọ nyocha nke ọma na-ewepụta narị narị ndị ga-ekekọta, mmuo ndabara na-abụkarị ịhazi usoro nke ọma site na ijikọ ike efu (D G kechie) ma ọ bụ akara ụgbọ mmiri. Agbanyeghị, ihe Nyochaa IJMS na nyocha ọba akwụkwọ peptide mebere na nkwado (2024) na-ekwusi ike na ọnụ ọgụgụ ọdụ ụgbọ mmiri na-edochaghị anya na-ahọrọkarị maka oke ikuku hydrophobic karịa eziokwu, kọntaktị electrostatic kpọmkwem na hydrogen-njikọ mmekọ. Onye nrụpụta nnwale peptide
Iji guzobe dị irè peptide kụrụ triage ọrụ, A ga-enyocharịrị n'usoro n'usoro n'usoro n'usoro n'usoro mmepe nke anụ ahụ iji mata ụgwọ njikọ nyocha peptide mgbakọ na mwepụ mmalite nchọpụta:
1. Njupụta kọntaktị ihu vs. Nkwakọ ngwaahịa Hydrophobic anaghị akọwapụta
Ọhụụ PPI nwere mmekọrịta dị elu na-adaberekarị na ntụpọ ọkụ hydrophobic (eg., Leu, Ya na, Phe, Trp fọdụrụ). Agbanyeghị, mgbe ihe ọkụkụ e buru n'amụma na-egosiputa maapụ kọntaktị hydrophobic na-aga n'ihu nke na-adaba ihe fọdụrụnụ anọ ma ọ bụ karịa., ike na-ebu maka ebumnuche Hexapeptide 2 njide bụ ihe a na-apụghị icheta n'anụ ahụ na ike na-akpali maka mkpakọrịta onwe onye. N'oge mgbako kụrụ triage, Ekwesịrị ịsacha maapụ kọntaktị iji mata ọdịiche nke netwọkụ hydrogen-bond ntụzịaka na àkwà mmiri nnu na patches na-abụghị polar..
2. Mpaghara elu enwere ike ịnweta mgbaze (UGBUA) na oge Hydrophobic
Onye na-eweta ụlọ ọrụ Peptides Na-enyocha oge hydrophobic (mu_H) na amphipathicity na-ekpughe ma a na-edobe residues hydrophobic n'otu ihu nke α-helix ma ọ bụ kesaa ya na-enweghị usoro n'ofe usoro.. Oge hydrophobic dị elu jikọtara ya na nnukwu ngụkọta nke SASA na-abụghị polar na-egosi na peptide ga-egosipụta ọchịchọ onwe nke amphipathic siri ike na sistemụ nchekwa mmiri., na-eduga na nchịkọta micellar ma ọ bụ fibrillar.
3. Net Charge na Isoelectric Point (pI) nhazi nhazi
Peptides nwere ụgwọ net dị nso na-anọpụ iche (ụgwọ net -1 ka +1) na physiological pH (pH 7.4) enweghị electrostatic repulsion agha. Enweghị mkparị Coulombic idobe ụdọ peptide n'otu n'otu na ngwọta, van der Waals na mmekọrịta hydrophobic na-achịkwa, ịkwọ ụgbọ mmiri ngwa ngwa na ịmepụta isi ụgwọ njikọ nyocha peptide mgbakọ na mwepụ.
| Oke Mpụta Mgbakọ | Nkọwa Nhazi Anụ ahụ | Mgbakọ Wet-Lab & Ijikwa ibu | Oke ihe omume Triage |
|---|---|---|---|
| D G kechie / Akara docking | Ike mmekọrịta ebumnobi buru amụma | Ịdabere n'elu na kọntaktị na-abụghị polar nwere ike kpuchie njide ma ọ bụ nchịkọta onwe ya | nyo n'elu 5% na-akụta megide akara mmepe |
| Kọntaktị Hydrophobic na-aga n'ihu | Ọhụụ na-ejikọ ọnụ na-abụghị polar agbatịkwuru | Inter-chain β-ibé akwụkwọ ndakpọ n'oge SPPS; insolubility post-cleavage | Ọkọlọtọ na-aga n'ihu na-agba ọsọ na-abụghị polar >4 foduru |
| Oge Hydrophobic (mu_H) | Nhazi nhazi nke Amphipathic | Nhazi micelle na-arụ ọrụ n'elu; colloidal assay nnyonye anya | Gbakọọ ikike amphipathic n'ofe ihu helical |
| Ụgwọ net na pH 7.4 | Ike nkwụsi ike elektrọstatic | Isoelectric ọdịda; Mgbasa mmiri dị ala na mgbasa ozi nyocha | Tulee ụgwọ ụgbụ n'etiti -1.0 na +1.0 |
| Mgbanwe RMSF azụ | Entropy conformational mpaghara | Ntaramahụhụ Entropic mgbe ejikọtara ya; loops na-enweghị nhazi floppy | Achọrọ nhazi nke abụọ kwụsiri ike tupu nhazi |
Ọrụ Njikọ Ahụ nke Mapi: Site na mbinye aka Silico gaa na ọdịda Wet-Lab
Iji gosi ka mbinye aka mgbakọ na-atụgharị gaa na mgbochi anụ ahụ, tụlee profaịlụ nke Peptide VB:
Profaịlụ onye ntuli aka Peptide VB:
- Ogologo Usoro: 22 amino asịd
- Ebumnuche: ngalaba njikọ PPI intracellular
- Amụma na Silico Affinity: K d = 14 nM (Δ G njikọ = -10.8 kcal/mol)
- Njirimara usoro: Nwere isi hydrophobic nke fọdụrụ 6 (
-Leu-Phe-Val-Trp-Ile-Leu-), pI gbakọọ $6.2$, a net ụgwọ nke $0$ na pH 7.4, na GRAVY (Nnukwu nkezi nke Hydropathicity) akara nke +0.68.
Ọ bụ ezie na Peptide VB na-anọchite anya mgbakọ pụtara pụtara ìhè, Profaịlụ usoro ya na-egosiputa ihe fọrọ nke nta ka ọ bụrụ ụgwọ ọ bụla kpochapụrụ maka njikọ kemịkalụ na nleba anya nke ndu. Enweghị enyemaka n'usoro, izipu Peptide VB ozugbo na ọkọlọtọ Fmoc-SPPS na-arụpụta ụdị ọdịda arụmọrụ siri ike:
Hit mebere: Peptide VB
▼ (Synthesis anaghị agbanwe agbanwe)
- Ọzịza ọzịza nke resin ► Mkpokọta β- mpempe akwụkwọ n'etiti yinye n'oge njikọta
- Ọdịda mkpochapụ ► Ọdịdị gel amorphous n'oge mkpochapụ TFA
- Ọcha ọcha ► Mgbasa elu kacha elu RP-HPLC siri ike (<35% crude ịdị ọcha)
- Ọdịda nyocha nke izizi ► mkpokọta mkpokọta na PBS (Ụgha adịghị mma / nsi)
1. Mkpokọta Inter-Chain β-Sheet N'oge SPPS
Ka peptide yinye na-agbatị na nkwado siri ike (eg., Wang ma ọ bụ Rink Amide resin), hydrophobic usoro dị ka -Leu-Phe-Val-Trp-Ile-Leu- motif na Peptide VB na-etolite netwọk β-sheet nwere njikọ n'etiti yinye hydrogen. Nke a onu, mara dị ka resin ọdịda ma ọ bụ "nchịkọta usoro siri ike," na-egbochi ọzịza resin nke ukwuu ma na-egbochi amino acid arụ ọrụ na-abata ịbanye na amine N-terminal.. Nsonaazụ bụ njikọta ezughị ezu, ọtụtụ usoro nhichapụ ($n-1, n-2$), ma belata nke ukwuu mkpụrụ crumb.
2. Mkpochapụ na ọdịda TFA
Mgbe emechara mgbakọ agbụ, Mwepu zuru ụwa ọnụ na mkpochapụ resin site na iji ngwakọta mmanya TFA ọkọlọtọ (eg., TFA / TIS / H₂O / EDT) kpughee ụdọ akụkụ hydrophobic echedoro nke ọma. Maka usoro motifs ịnya ụgbọ ala hydrophobic patches peptide mkpokọta, Mwepụ nke ichebe iche iche na-ewepụ nnukwu ihe dị egwu nke gbochiri mmekọrịta onwe onye na mbụ. Mgbe ị na-atụba ihe mgbawa ahụ, gbachaa n'ime mmiri oyi na-atụ diethyl ether, Peptide VB na-etolite ihe na-adịghị edozi, rubbery precipitate ma ọ bụ emulsion na-adịgide adịgide nke enweghị ike ikewapụ ya nke ọma site na centrifugation.
3. Aqueous Insolubility na Assay Artifacts
Ọbụlagodi na a na-asachapụ obere Peptide VB nke ọma site na nkwadebe Reverse-Phase High- Performance Liquid Chromatography (RP-HPLC), pI na-anọpụ iche na akara GRAVY dị elu pụtara na ọ chọrọ nnukwu ihe mgbaze organic (eg., >20% DMSO) ịnọgide na ngwọta. A Ọmụmụ ACS na nkwụsị azụ azụ peptide na njedebe nchịkọta (2018) gosiputara na solubility mmiri dị elu na-ejikọta ya na obere oge a na-etinye na ụyọkọ jikọtara onwe ya.. Mgbe etinyere ya n'ime ihe nchekwa ihe nyocha nke mmiri (dị ka PBS na pH 7.4), peptides hydrophobic na-enweta obere mmiri ozuzo ma ọ bụ na-emepụta mkpokọta colloidal, na-ekwenye ekwenye na-ejikọta kinetics, ugha-mma mgbochi, ma ọ bụ mmebi akpụkpọ ahụ na-abụghị nke akọwapụtara na nyocha nke sitere na cell.
Ịsụgharị n'ime amụma Silico ka ọ bụrụ Mgbanwe Kemịkalụ Ezubere iche
Kama ịhapụ nnukwu mmekọrịta dị ka Peptide VB, ndị nchọpụta nwere ike itinye mgbanwe kemịkalụ strategic n'oge imewe usoro iji merie ụgwọ njikọ nyocha peptide mgbakọ na mwepụ. Mgbanwe ndị a na-echekwa ihu na-ejikọta ebumnuche dị mkpa ma na-ebelata ụgwọ anụ ahụ. Ijikọta atumatu ndị a n'ime atụmatụ njikọta bụ isi nke usoro ọrụ dị irè maka ijikọ igwe mmụta peptide amụma na usoro ụlọ nyocha dị njikere.
Mgbakọ kụrụ Triage
Ịkwụsị ụgwọ ọrụ nkwekọrịta nkwekọrịta • Poly-Lys/Arg Tags • Hydrocarbon Stapling • O-Acyl Isopeptides (i, i+4 / i, i+7) • Nchekwa azụ • Macrocyclization
Assay Readout mkpa • N/C-Terminal Biotin • Fluorophores (FITC/Cy5) • Ahx Linker Spacers
1. Nkwalite Solubility site na Peptide Solubility Tags na Nhọrọ Stapling
Mgbe nyocha mgbakọ na mwepụ na-achọpụta ihe ọkụkụ nwere oke hydrophobicity ma ọ bụ ụgwọ net na-anọpụ iche, Ekwesịrị itinye mgbanwe na-edozi ahụ ozugbo na atụmatụ SPPS. Na-ejikọta peptide solubility mkpado na stapling teknụzụ na-enye ngwọta abụọ maka njikwa na nkwụsi ike nhazi:
- Tags Poly-Cationic nwere ike ihicha (Poly-Lys / Poly-Arg): Na-agbakwunye mkpado hydrophilic nwa oge-dị ka penta-lysine (K₅) ma ọ bụ hexa-arginine (R₆) usoro-na C-terminus ma ọ bụ N-terminus site na isi-labile ma ọ bụ njikọ enweghị ntụpọ na-agbanwe nke ọma profaịlụ nke peptide.. Nchọpụta JACS na mkpado njikọ njikọ poly-cationic nwere ike ihichapụ (2024) kwadoro na mkpado poly-cationic na-egbochi nchịkọta dabere n'usoro n'oge mgbakọ agbụ na resin ma nọgide na-enwe ike dị elu n'oge nkwụsị TFA na nchacha RP-HPLC.. Na-eso sachaa, nkenke ọgwụgwọ na aqueous isi (ma ọ bụ enzymatic cleavage) na-ewepụ mkpado ahụ na-enweghị ntụpọ, na-enye usoro nke nwa afọ na ịdị ọcha dị elu.
- O-Acyl Isopeptide Nchekwa Ọkpụkpụ: Maka usoro nke nwere ike ịnweta nchịkọta β-ibé akwụkwọ n'etiti agbụ n'oge SPPS, iji nkeji O-acyl isopeptide dochie isi Serine ma ọ bụ threonine, na-ahazi ọkpụkpụ azụ peptide site na njikọ amide na njikọ ester.. Nke a na-ewebata kink ihe nhazi nke na-akpaghasị mbukota β-ibé na resin. Mgbe njikọta na ịdị ọcha na pH acidic, incubating peptide dị ọcha na ihe nchekwa nyocha na-anọpụ iche (pH 7.4) na-akpalite a quantitative, O → N mgbanwe acyl nke na-eweghachi azụ azụ peptide nke ala.
2. Nkwụsi ike Conformational: Hydrocarbon Stapling & Ịgba ígwè
peptides linear na-agbanwe agbanwe na-atakarị ahụhụ site na ntaramahụhụ entropic dị elu mgbe ejikọtara ya, ngwa ngwa proteolytic mmebi na serum (t 1/2 < 15 min), na ikpughe nke hydrophobic backbone amides na-akwalite hydrophobic patches peptide mkpokọta.
- Hydrocarbon Stapling ($i, i+4 na $i, i+7$): Site na dochie amino acid abụọ na-adịghị mkpa dị na ihu na-adịghị ejikọta α-helix na α na-abụghị nke okike., Amino asịd α-nwere mgbagha nwere agbụ akụkụ olefinic (eg., S₅ ma ọ bụ R₈), ruthenium-catalyzed mgbanaka-emechi metathesis (RCM) na-emepụta ihe niile-hydrocarbon crosslink ("Staple"). Stapling na-akpọchi peptide n'ime nhazi α-helical na-arụ ọrụ, na-echebekwa njikọ amide nke azụ site na mgbawa protease, ma nwee ike melite cell-permeability mgbe ị na-ebelata mkpokọta na-abụghị nke akọwapụtara.
- Isi-na-Ọdụ & Akụkụ-Chain Macrocyclization: Ịtụgharị linear hits n'ime usoro cyclic site na disulfide bond, lactam àkwà mmiri, ma ọ bụ njikọ thioether na-amachibido nnwere onwe ime mgbanwe, na-egbochi peptide ịnakwere ogologo β-strand geometries nke na-eme ka amyloid dị ka fibrillization..
3. Ndozigharị Peptide dị njikere: Ịkpọ aha saịtị akọwapụtara & Ndị oghere oghere
Ịga ngwa ngwa site na njikọ gaa na nyocha biochemical (eg., Mgbapụta Plasmon dị n'elu [SPR], Interferometry bio-Layer [GỤỌ], ma ọ bụ Fluorescence Polarization [FP]), peptide kwesịrị ịga nke ọma ngbanwe peptide dị njikere. Agbanyeghị, Ịtụnye nnukwu fluorophore ma ọ bụ biotin molecule ozugbo n'akụkụ ngalaba njikọ nwere ike imebi njikọ aka.. Dipeptide
- Ntinye nke Linkers na-agbanwe agbanwe (Ahx / PEG_4): Ịwụnye na-anọpụ iche, spacer na-agbanwe agbanwe dị ka 6-aminohexanoic acid (Ahx) ma ọ bụ obere polyethylene glycol (PEG_4) aka n'etiti peptide njedebe na mkpado arụ ọrụ na-eme ka nkewa dị n'ọgbara anya, na-egbochi mgbochi siri ike n'oge ejigide ebumnuche.
- Labeling regioselect: Njikọ biotin ma ọ bụ fluorescein isothiocyanate (FITC) na resin site na orthogonal echebe otu atụmatụ (eg., Lys(Mt) ma ọ bụ Lys(Alloc)) ekwe nkwa 100% arụ ọrụ kpọmkwem saịtị tupu ihichapụ ikpeazụ, na-emecha ngbanwe peptide dị njikere usoro.
Amụma n'ibu Silico Usoro nhazi Atụmatụ mgbanwe kemịkalụ akwadoro Isi Synthesis & Uru nyocha Hydrophobicity dị elu / Solubility dị ala Enweghị ngwọta polar; pI na-anọpụ iche Mkpado poly-Lysine/Arginine nwa oge site na njikọ ntọala-labile Na-egbochi ndakpọ resin; na-eme ka HPLC dị ọcha na mgbasa ozi aqueous On-Resin β-Ibe mpempe akwụkwọ Inter-chain azụ ọkpụkpụ hydrogen bonding O-Acyl Isopeptide ma ọ bụ Pseudoproline dipeptides na saịtị Ser/Thr/Pro Na-emebi usoro nke abụọ n'oge SPPS; na mberede O → N mgbanwe mgbe emechara ọcha Proteolytic Akwụsịghị & Entropy dị elu Ọkpụkpụ azụ ahịrị floppy; ngwa ngwa protease Hydrocarbon stapling ($i, i+4$ ma ọ bụ $i, i+7$ olefin metathesis) Haziri α-helix nọ n'ọrụ; enhances serum ọkara ndụ (t 1/2) na nnabata cell Mgbakọ Conformational dị elu Mgbanwe ọnụ ọnụ na-enweghị mmachi Disulfide, lactam, ma ọ bụ thioether macrocyclization Na-egbochi mgbanwe ọkpụkpụ azụ; na-ewepu conformations nke fibril Ihe mgbochi nke Steric / Ntinye aka Mgbakwunye akara ndị buru ibu na interface njikọ Njikọ ọnụ ọnụ regioselective site na ndị njikọ Ahx ma ọ bụ PEG_4 na-agbanwe agbanwe Na-echekwa mmekọrita ebumnuche (K d); na-enye aka-njikere readout aka
Nyocha nyocha & Njikwa ogo maka ịdị njikere nyocha
Onye na-eweta ụlọ ọrụ Peptides Atụmatụ mgbanwe emebere iji kpochapụ ụgwọ njikọ nyocha peptide mgbakọ na mwepụ bụ naanị siri ike ka nkwenye nyocha ya. Inweta ezigbo ihe nyocha peptide dị njikere chọrọ usoro njikwa mma siri ike nke na-akwado iguzosi ike n'ezi ihe nhazi, ịdị ọcha, na nnwere onwe pụọ n'ihe ndị na-emerụ emerụ.
Synthesis ezubere iche & Mgbanwe
Nyocha RP-HPLC ► Nkwenye ịdị ọcha (≥95%-98% Mpaghara N'okpuru usoro) ESI-MS dị elu } Monoisotopic Mass & Klas nkwenye mgbanwe 100 Nhazi ụlọ dị ọcha } Njikwa Endotoxin (<0.5 EU/mg) maka Bioassays
1. Mass Spectrometry dị elu (HRMS/ESI-MS)
Batch ọ bụla emepụtara ga-enwerịrị nkwenye monoisotopic mass site na Electrospray ionization Mass Spectrometry. (ESI-MS) ma ọ bụ Matrix-enyere Laser Desorption/Ionization Time-of-Flight (MALDI-TOF). Maka ndị chọrọ ime gbanwetụrụ nwere staples hydrocarbon, disulfides cyclic, ma ọ bụ biotin/fluorophore conjugates, Mwapụta nke MS ma ọ bụ nyocha uka dị elu na-akwado stoichiometry kemịkalụ ziri ezi ma na-ewepụ mgbanwe mgbanwe ezughị ezu..
2. Profaịlụ ịdị ọcha nke RP-HPLC nyocha
Nnwale njide nke mbụ na ọmụmụ ihe nhazi chọrọ ihe dị oke ọcha (≥ 95% ma ọ bụ ≥ 98% ịdị ọcha nke HPLC AUC na 220 nm na 280 nm). Profaịlụ RP-HPLC nyocha Kpv kwesịrị igosi nkọ, elu symmetrical na-enweghị nnukwu mmetọ ubu na-egosi diastereomers, usoro nhichapụ, ma ọ bụ oligomers soluble.
3. Ijikwa sterile na nkọwapụta Endotoxin dị ala
Maka nyocha ntụgharị mgbama dabere na cell ma ọ bụ ọmụmụ ọgwụ ọgwụ vivo, nkwadebe peptide emebere na gburugburu ebe a na-achịkwaghị achịkwa nwere ike ibute nje lipopolysaccharides. (LPS / endotoxins). Endotoxins na-ebute ndị na-anabata ihe na-abụghị nke akọwapụtara (TLR4) ịgbalite, na-eduga na nsị cellular na data ụgha. Na-emepụta peptides n'ime klaasị 100 Gburugburu ebe obibi dị ọcha nke na-adịghị ọcha na-eme ka ọkwa endotoxin dị n'okpuru ọnụ ụzọ biopharmaceutical siri ike. (<0.5 EU/mg).
Na-eme ka nkwalite ụzọ Peptide dị ngwa ngwa: Ụkpụrụ omume ebutere ụzọ
Site na iji mgbanwe kemịkalụ pụrụiche jikọtara metrik imewe, Ndị otu nyocha biopharma nwere ike iwepụ usoro nnwale na njehie nke na-akwụsịkarị mkpọsa peptide..
• Nweta ọkwa site na ΔG na-ekekọta yana kọntaktị maapụ nkwado. • Nzacha megide ebe elu hydrophobic, GRAVY, na ụgwọ net. • Họrọ mkpado solubilizing cleavable maka nnukwu hydrophobic hits.
Nzọpụ ụkwụ ọrụ PEPTIDE ebutere ụzọ 1: Ntụpụ ụkwụ NTỤTA KPỤTA KPỌTA 2: N'ỊMAPỤ ỤMỤ SILICO • Chọpụta ọsọ ọsọ na-abụghị polar na-aga n'ihu (>4 foduru). • Buru amụma nchikota resin na ihe egwu enweghị ike ime. Ntụpụ ụkwụ 3: Ezubere iche maka mgbanwe kemịkalụ • Webata staples hydrocarbon (i, i+4) maka floppy α-helices. • Debe akara Biotin/FITC nwere oghere Ahx na-agbanwe agbanwe. Ntụpụ ụkwụ 4: Ọkachamara SYNTHESIS & Nnwale nyocha nke CoA • Mezue Fmoc-SPPS site na iji matrices resin pụrụ iche.. • Kwado site na RP-HPLC (≥95%+), ESI-MS, na nyocha nke endotoxin.
Ịsụgharị hits mebere dị ka Peptide VB ka ọ bụrụ anụ ahụ, Nduzi dị njikere nyocha chọrọ onye mmekọ nke nwere ike ime mgbanwe mgbanwe kemịkalụ dị mgbagwoju anya n'ụkpụrụ dị elu nke ịdị ọcha na njikwa adịghị mma..
Site anyị pụrụ iche nnyocha na n'ichepụta ikpo okwu, njikọ peptide omenala na ọrụ mgbanwe pụrụ iche na MOL Mgbanwe na-enye ndị otu biopharma nkwado ngwụcha ruo ọgwụgwụ-site na usoro mbido na usoro mgbanwe gaa na Klas. 100 mmepụta ihe adịghị mma, omenala solubilizing mkpado echichi, macrocyclization, yana Asambodo nyocha HPLC/MS zuru oke (CoA) akwụkwọ.
Site n'ijikọ amụma mgbakọ na mwepụ ahaziri ahazi site na ụbọchị mbụ, ndị na-eme nchọpụta nwere ike iji obi ike kwalite ndị na-eme atụmatụ peptide kachasị mma n'ime nyocha nyocha ngwa ngwa, na obi ike dị elu, na ebelata nke ukwuu iteration ụgwọ.
