Lits'oants'o tsa Peptide tsa Computational: Lintho tsa Pele tsa Synthesis
Tlhahlobo ea maemo a holimo, AI e hlahisang, le lipapiso tsa matla a limolek'hule li fetotse haholo ho sibolloa ha peptide ea pele. Li-platform tsa sejoale-joale tsa computational li ka lekola tatellano ea batho ba limilione ka lihora tse ngata, ho etelletsa pele ho otla ho ipapisitsoe le matla a mahala (D G tlama), ho kopana ha sefahleho, le boikhethelo bo boletsoeng esale pele. Leha ho le joalo, lihlopha tsa lipatlisiso tsa biopharmaceutical hangata li kopana le bothata bo ferekanyang ha li tloha ho lihlahisoa tsa silico ho ea ho netefatso ea 'mele ea lab: maemo a holimo a holimo hangata a bonahala a le thata ho a kopanya, hloekisa, kapa qhala litlhahlobong tsa mantlha tsa bioloji.
Peptide e ntlafalitsoeng ka komporo e holimo 0.1% ea skrineng ea sebele e ka hloleha habonolo nakong ea synthesis ea peptide e tiileng (SPSS) ka lebaka la ho kopanya diketane tsa mokokotlo, ho kenella ka har'a gel e sa tsitsang nakong ea asiti ea trifluoroacetic (TFA) qhetsola, kapa ho theha likopano tsa colloidal tse hlahisang matšoao a fosahetseng litekong tsa tlhahlobo. Ho rarolla likhohlano tsena ho hloka ho fetela ka nģ'ane ho ho rarolla mathata ka morao ho hoc. Biopharma R&Lihlopha tsa D li tlameha ho amohela sehlopha se kopaneng peptide hit triage workflow e hlahlobang computational peptide screening synthesis liabilities pele o fana ka tatellano ho synthesizer resin.
Ka ho hlahloba "Peptide VB" -e leng moemeli oa 22-mer computational hit moenjineri ho lebisa tšebelisano ea protheine le protheine. (PPI) interface-sengoloa sena se hlalosa moralo oa liqeto o etelletsoeng pele. Re hlahloba mokhoa oa ho hlalosa mekhoa ea likhokahano ea khomphutha, 'mapa o boletse esale pele mekoloto ea 'mele joalo ka li-patches tsa hydrophobic le kotsi ea ho bokellana, le ho fetolela likhakanyo tseo ka liqeto tsa konkreite tsa motsoako oa lik'hemik'hale-ho kenyeletsoa le li-tag tsa solubilizing, tlhahiso ea hydrocarbon, le ho ngolla sebaka se ikhethileng-ho fana ka lisebelisoa tse lokisitsoeng ka potlako le ka liteko tse fokolang.
Mabapi le Mongoli:
Dr. Aris Vance, Ph.D. | Ofisiri e ka Sehloohong ea Mahlale & Hlooho ea Peptide Chemistry ho MOL Changes
Dr. Vance e fihlile 18 lilemo tsa boiphihlelo moralong o utloahalang oa lithethefatsi, solid-phase peptide synthesis (SPSS), le computational hit triage. O etella pele sehlopha sa lipatlisiso le nts'etsopele ho MOL Changes, likhakanyo tsa ho ithuta ka mochini ka mokhoa o ikhethileng oa ho kopanya lik'hemik'hale le Sehlopha 100 tlhahiso e nyopa.
Computational Hit Triage: Decoding Interfacial Contact Paterone & Melemo ea Sebopeho
Ha lilaebrari tsa tlhahlobo ea sebele li fana ka makholo a batho ba tlang ho tlama, maikutlo a kamehla a tlhaho hangata ke ho beha maemo a tatellano ka ho tlama matla a mahala (D G tlama) kapa lintlha tsa ho emisa. Leha ho le joalo, e Tlhahlobo ea IJMS mabapi le tlhahlobo ea laeborari ea peptide le netefatso (2024) e hatisa hore lintlha tse sa hloekisoang tsa docking hangata li khetha sebakeng se feteletseng sa hydrophobic ho fapana le 'nete, likhokahano tse tlatsanang tsa electrostatic le hydrogen-bonding. Moetsi oa Teko ea Peptide
Ho theha e atlehang peptide hit triage workflow, liphetho tsa khomphutha li tlameha ho hlahlojoa ka mokhoa o hlophisehileng khahlano le maemo a ntlafatso ea 'mele ho khetholla computational peptide screening synthesis liabilities qalong ea ho sibolloa:
1. Interfacial Contact Density vs. Ho Paka ha Hydrophobic e sa Tobang
Likamano tse phahameng tsa PPI hangata li itšetlehile ka libaka tse chesang tsa hydrophobic (mohlala, Leu, Ka, Phe, Trp mesaletsa). Leha ho le joalo, ha pina e boletsoeng esale pele e bonts'a 'mapa o kopaneng oa hydrophobic o nkang masalela a mane kapa ho feta a latellanang, matla a ho kganna bakeng sa sepheo Hexapeptide 2 ho tlama ho ke ke ha khetholloa ka 'mele ho matla a ho khanna bakeng sa ho ikamahanya. Nakong ea tlhahlobo ea tlhahlobo ea mali, limmapa tsa ho ikopanya li lokela ho hloekisoa ho khetholla marang-rang a hydrogen-bond le marokho a letsoai ho tloha ho li-patches tse se nang polar..
2. Solvent-Accessible Surface Area (HONA JOALE) le Hydrophobic Moment
Mofani oa Fektheri ea Peptides Ho lekola motsotso oa hydrophobic (mu_H) mme amphipathicity e senola hore na masala a hydrophobic a arotsoe ka sefahleho se le seng sa α-helix kapa a ajoa ka tšohanyetso ho pholletsa le tatellano.. Motsotso o phahameng oa hydrophobic o kopantsoeng le mats'oao a SASA a mangata a se nang polar a hore peptide e tla bonts'a litloaelo tse matla tsa ho ikamahanya le amphipathic lits'ebetsong tsa buffer tse nang le metsi., e lebisang ho micellar kapa fibrillar aggregation.
3. Net Charge le Isoelectric Point (pI) Tekanyetso
Li-peptides tse nang le tefiso e haufi le ho se nke lehlakore (net charge -1 ho +1) ka pH ea fisioloji (pH 7.4) ho hloka matla a ho leleka electrostatic. Ntle le ho halefisoa ke Coulombic ho boloka liketane tsa peptide ka bomong li arohane ka tharollo, van der Waals le likamano tsa hydrophobic li laola, ho kganna pula ka potlako le ho bopa tse kgolo computational peptide screening synthesis liabilities.
| Computational Output Parameter | Tlhaloso ea Sebopeho sa 'Mele | Tšimoloho ea Lab e Metsi & Ho sebetsana le Boikarabelo | Triage Action Threshold |
|---|---|---|---|
| D G tlama / Lintlha tsa Docking | Tšebelisano e boletsoeng esale pele ea matla | Ho itšetleha haholo ka likhokahano tse se nang polar ho ka pata ho tlama ha sepheo kapa ho ipokella | Sefe holimo 5% otla kgahlanong le dintlha tsa ntshetsopele |
| Mabitso a Contiguous Hydrophobic | Khokahano e atolositsoeng e sa tlanngoeng ke polar | Inter-chain β-sheet e putlama nakong ea SPPS; ho se qhibidihe ka mora ho phunya | Tlaleha mathateng a sa polar >4 masalla |
| Motsotso oa Hydrophobic (mu_H) | Amphipathic structural alignment | Sebopeho sa li-micelle tse sebetsang holimo; tšitiso ea tlhahlobo ea colloidal | Bala tšekamelo ea amphipathic ho pholletsa le lifahleho tsa helical |
| Chelete e felletseng ho pH 7.4 | Matla a ho tsitsisa a electrostatic | Pula ea Isoelectric; ho qhibiliha ha metsi a tlase mecheng ea litaba tsa tlhahlobo | Tlaleha litefiso tse ngata pakeng tsa -1.0 le +1.0 |
| Mokokotlo oa RMSF Flexibility | Conformational entropy ea lehae | Kotlo ea Entropic ha e tlama; floppy loops e sa hlophisoang | E hloka tlhophiso e tsitsitseng ea bobeli ea sebopeho sa pele |
Ho etsa 'mapa oa Melato ea Physical Synthesis: Ho tloha ho Silico Signatures ho ea ho Wet-Lab Failures
Ho hlakisa hore na li-signature tsa computational li fetolela joang litšitiso tsa 'mele, nahana ka boemo ba Peptide VB:
Boemo ba Mokhethoa oa Peptide VB:
- Bolelele ba Tatelano: 22 li-amino acid
- Sepheo: Sebaka se tlamang sa Intracellular PPI
- E boletsoeng esale pele ka Silico Affinity: K d = 14 nM (Δ G tlama = -10.8 kcal / mol)
- Tatelano Litšobotsi: E na le 6-residu hydrophobic core (
-Leu-Phe-Val-Trp-Ile-Leu-), pI e baloang ea $6.2$, chelete e ngata ea $0$ ka pH 7.4, le GRAVY (Karolelano e kholo ea Hydroropathicity) lintlha tsa +0.68.
Le ha Peptide VB e emela pina e ikhethang ea computational, boemo ba eona ba tatelano bo bontša hoo e batlang e le molato o mong le o mong oa khale oa motsoako oa lik'hemik'hale le tlhahlobo ea baeloji. Ntle le ho kenella ka sebopeho, ho romela Peptide VB ka kotloloho ho Fmoc-SPPS e tloaelehileng e fana ka mekhoa e matla ea ho hloleha ha ts'ebetso:
Virtual Hit: Peptide VB
▼ (Motsoako o sa fetotsoeng)
- Ho Hlōleha ho Ho ruruha ha Resin ► Ho kopanya β-sheet ka har'a ketane nakong ea ho kopanngoa
- Pula ea Cleavage ► Ho etsoa ha li-gel tsa amorphous nakong ea TFA cleavage
- Tlhoekiso e Hloekileng ► Katoloso e matla ea tlhoro ea RP-HPLC (<35% bohloeki bo sa hloekang)
- Ho hloleha ha Tekolo ea Mantlha ► Ho kopanya Colloidal ho PBS (Phoso ea bohata / chefo)
1. Kopano ea Inter-Chain β-Sheet Nakong ea SPPS
Ha ketane ea peptide e ntse e hola holim'a tšehetso e tiileng (mohlala, Wang kapa Rink Amide resin), tatellano ea hydrophobic joalo ka -Leu-Phe-Val-Trp-Ile-Leu- motif ho Peptide VB e theha marang-rang a pharaletseng a li-inter-chain hydrogen-bonded β-sheet. Ketsahalo ena, e tsejoang ka hore ke resin collapse kapa “matla a tatellano a thata,” e thibela haholo ho ruruha ha resin le ho thibela li-amino acid tse kenang hore li se ke tsa fihlella N-terminal amine.. Sephetho ke ho kopanya ho sa fellang, tatellano e batsi ya ho hlakolwa ($n-1, n-2$), le ho fokotsa haholo lihlahisoa tse tala.
2. TFA Cleavage le Pula
Ha ho phetheloa kopano ea ketane, Tšireletso ea lefats'e le ho petsoha ha resin ho sebelisa motsoako o tloaelehileng oa li-cocktail tsa TFA (mohlala, TFA / TIS / H₂O / EDT) pepesa liketane tse ka thōko tsa hydrophobic tse sirelelitsoeng ka botlalo. Bakeng sa tatellano motifs ho khanna hydrophobic patches peptide aggregation, ho tlosoa ha lihlopha tse sireletsang ho felisa bongata ba steric boo pele bo neng bo thibela ho ikopanya. Ha o theola cleavage filtrate ka har'a diethyl ether e batang, Peptide VB e etsa ntho e sa tsitsang, rubbery precipitate kapa emulsion e tsitsitseng e ke keng ea aroloa ka mokhoa o hloekileng ka centrifugation.
3. Aqueous Insolubility le Assay Artifacts
Leha palo e nyane ea Peptide VB e ka hloekisoa ka katleho ka mokhoa o lokiselitsoeng oa Reverse-Phase High-Performance Liquid Chromatography. (RP-HPLC), PI ea eona e sa nke lehlakore le lintlha tse phahameng tsa GRAVY li bolela hore e hloka metsoako e phahameng ea li-co-solvents (mohlala, >20% DMSO) ho dula tharollong. An Thuto ea ACS mabapi le tharollo ea mokokotlo oa peptide le meeli ea ho kopanya (2018) e bontšitse hore ho qhibiliha ho hoholo ha metsi ho amana ka kotloloho le nako e fokotsehileng e sebelisoang ho lihlopha tse ikopantseng.. Ha e hlapollotsoe ka har'a li-buffers tsa tlhahlobo tsa mantlha tse nang le metsi (joalo ka PBS ho pH 7.4), Li-peptide tsa hydrophobic li na le pula e nyane kapa li etsa li-colloidal aggregates, ho fana ka kinetics e tlamang e sa tsitsang, thibelo e ntle ya bohata, kapa tšitiso e sa tobang ea lera litlhahlobong tse thehiloeng ho lisele.
Ho Fetolela Likhakanyo tsa In Silico ho Liphetoho tse Lebisitsoeng tsa Lik'hemik'hale
Sebakeng sa ho lahla likotlo tse phahameng joalo ka Peptide VB, bafuputsi ba ka sebelisa liphetoho tsa leano la lik'hemik'hale nakong ea moralo oa tatellano ho hlola computational peptide screening synthesis liabilities. Liphetoho tsena li boloka sefahleho sa bohlokoa se tlamang sepheo ha li ntse li fokotsa likoloto tsa 'mele. Ho kopanya maqheka ana ho moralo oa ho kopanya ho theha motheo oa ts'ebetso e sebetsang hantle bakeng sa likhakanyo tsa peptide tsa ho ithuta ka mochini ho latela tatellano e lokiselitsoeng lab.
Computational Hit Triage
Solubility Liability Conformational Liability • Poly-Ls/Arg Tags • Hydrocarbon Stapling • O-Acyl Isopeptides (ke, ke+4 / ke, ke +7) • Tšireletso ea Mokokotlo • Macrocyclization
Litlhoko tsa ho Bala Litlhahlobo • N/C-Terminal Biotin • Fluorophores (FITC/Cy5) • Ahx Linker Spacers
1. Ntlafatso ea Solubility ka Li-tag tsa Solubility ea Peptide le Likhetho tsa Stapling
Ha tlhahlobo ea komporo e supa ho otla ka hydrophobicity e feteletseng kapa tefiso e sa nke lehlakore, Liphetoho tsa solubilizing li lokela ho kenyelletsoa ka kotloloho ho morero oa SPPS. Ho kopanya li-tag tsa ho qhibiliha ha peptide le stapling mahlale a fana ka tharollo e habeli bakeng sa ho sebetsana le botsitso ba sebopeho:
- Cleavable Poly-Cationic Tags (Poly-Ls / Poly-Arg): Ho hokela tag ea nakoana ea hydrophilic-joalo ka penta-lysine (K₅) kapa hexa-arginine (R₆) tatelano - ho C-terminus kapa N-terminus ka base-labile kapa traceless linker e fetola haholo boemo ba tharollo ea peptide.. Patlisiso ea JACS mabapi le li-tag tsa poly-cationic synthesis tse qhekellang (2024) e netefalitse hore li-tag tsa poly-cationic li thibela ho kopana ho itšetlehileng ka tatellano nakong ea kopano ea ketane ho resin le ho boloka ho qhibiliha ho hoholo nakong ea tlhoekiso ea TFA le tlhoekiso ea RP-HPLC.. Ho latela tlhoekiso, phekolo e khutšoanyane ka setsi sa metsi (kapa ho phatloha ha enzymatic) e tlosa letshwao ntle le ho hlaka, ho fana ka tatelano ya matsoalloa ka bohloeki bo hodimo.
- Tšireletso ea mokokotlo oa O-Acyl Isopeptide: Bakeng sa tatelano e atisang ho kopanngoa ka har'a ketane ea β-sheet nakong ea SPPS, ho khutlisa masala a bohlokoa a Serine kapa Threonine ka li-O-acyl isopeptide ho hlophisa bocha mokokotlo oa peptide ho tloha ho tlamahano ea amide ho ea ho khokahano ea ester.. Sena se hlahisa kink ea sebopeho e sitisang 'mele ho paka β-sheet holim'a resin.. Ka mor'a synthesis le tlhoekiso ka acidic pH, ho kenya peptide e hloekisitsoeng ka har'a buffer ea tlhahlobo e sa nke lehlakore (pH 7.4) e baka bongata, ka tšohanyetso O → N acyl shift e khutlisetsang mokokotlo oa letsoalloa oa peptide.
2. Ho tsitsisa ha Conformational: Hydrocarbon Stapling & Ho tsamaea ka baesekele
Li-peptide tse bonolo tsa linear hangata li na le likotlo tse phahameng tsa entropic ha li tlama, ho senyeha ha proteolytic ka potlako serum (t 1/2 < 15 min), le ho pepeseha ha li-amide tsa mokokotlo oa hydrophobic tse khothalletsang hydrophobic patches peptide aggregation.
- Hydrocarbon Stapling ($ke, i+4$ le $i, ke+7$): Ka ho nkela li-amino acid tse peli tseo e seng tsa bohlokoa tse fumanehang sefahlehong se sa tlameng sa α-helix ka α eo e seng ea tlhaho., α-disubstituted amino acid tse nang le liketane tsa mahlakoreng a olefinic (mohlala, S₅ kapa R₈), metathesis e koalang lesale la ruthenium-catalyzed (RCM) e theha sehokelo sa hydrocarbon tsohle ("tse ka sehloohong"). Stapling e notlela peptide hore e be α-helical conformation e sebetsang, e sireletsa mokokotlo oa li-amide bond ho tsoa ho protease cleavage, mme e ka ntlafatsa ho kenella ha lisele ha e ntse e fokotsa ho kopanya ho sa totobalang.
- Hlooho-ho-Mohatla & Macrocyclization ea Side-Chain: Fetolela linear hits ho li-cyclic bond ka disulfide bond, marokho a lactam, kapa likhokahano tsa thioether li thibela tokoloho ea ho lumellana, ho thibela peptide ho amohela lijeometri tse atolositsoeng tsa β-strand tse tsamaisang fibrillization ea amyloid..
3. Phetoho ea Assay Ready Peptide: Ho Ngola ka ho Iketla ha Sebaka & Spacers
Ho tsamaea ka potlako ho tloha ho synthesis ho ea litekong tsa biochemical (mohlala, Sefate sa Plasmon Resonance [SPR], Interferometry ea Bio-Layer [PHETHA], kapa Fluorescence Polarization [FP]), Peptide e tlameha ho tsamaea hantle Assay itokiselitse phetoho ea peptide. Leha ho le joalo, ho beha molek'hule ea fluorophore kapa biotin ka kotloloho haufi le sebaka se tlamang ho ka sitisa boitlamo ba sepheo.. Dipeptide
- Kenyelletso ea Flexible Linkers (Ahhh / PEG_4): Ho kenya ho se nke lehlakore, flexible spacer joalo ka 6-aminohexanoic acid (Ahhh) kapa polyethylene glycol e khutšoanyane (PEG_4) sebetsana pakeng tsa terminus ea peptide le tag e sebetsang e tiisa karohano ea sebaka, ho thibela tšitiso ea steric nakong ea ho tlama ha sepheo.
- Regioselective Labeling: Ho kopanya biotin kapa fluorescein isothiocyanate (FITC) holim'a resin ka mekhoa ea ho sireletsa lihlopha tsa orthogonal (mohlala, Lys(Mtt) kapa Lys(Alloc)) tiisetso 100% ts'ebetso e ikhethileng ea sebaka pele ho qhetso ea ho qetela, ho phethela Assay itokiselitse phetoho ea peptide tshebetso.
E boletsoeng esale pele ka Boikarabelo ba Silico Mokhoa oa Sebopeho Leano la Phetoho ea Lik'hemik'hale tse khothalelitsoeng Tšimoloho ea Pele & Melemo ea Assay Hydrophobicity e phahameng / Tlase Sollubility Ho hloka tharollo ea polar; ho se nke lehlakore pI Letlapa la nakoana la poly-Lysine/Arginine ka base-labile linker E thibela ho putlama ha resin; e nolofalletsa ho hloekisoa ha HPLC mecheng ea litaba tse nang le metsi On-Resin β-Sheet Aggregation Inter-chain backbone hydrogen bonding O-Acyl Isopeptide kapa Pseudoproline dipeptides libakeng tsa Ser/Thr/Pro E senya sebopeho sa bobeli nakong ea SPPS; ka boithatelo O→ N chencha ka mor'a tlhoekiso Ho hloka botsitso ha Proteolytic & Entropy e phahameng Floppy linear mokokotlo; phihlello e potlakileng ya protease Hydrocarbon stapling ($ke, i+4$ kapa $i, i+7$ olefin metathesis) E hlophisa esale pele α-helix e sebetsang; e ntlafatsa halofo ea bophelo ba serum (t 1/2) le ho nkela lisele Phahamiso e Phahameng ea Conformational Phetoho e sa lekanyetsoang ea terminal Disulfide, lactam, kapa thioether macrocyclization E thibela ho tenyetseha ha mokokotlo; e felisa li-conformations tse tloaelehileng tsa fibril Thibelo ea Assay Steric / Tšitiso Khokahano e tobileng ea lileibole tse ngata ho sehokelo se tlamang Regioselective terminal conjugation ka lihokelo tse feto-fetohang tsa Ahx kapa PEG_4 E boloka kamano ea sepheo (K d); e fana ka lithupa tse lokiselitsoeng ho bala
Netefatso ea Analytical & Taolo ea Boleng bakeng sa Boikemisetso ba Tekolo
Mofani oa Fektheri ea Peptides Leano la ho fetola le reretsoeng ho felisa computational peptide screening synthesis liabilities e matla feela joalo ka netefatso ea eona ea tlhahlobo. Ho fana ka thepa ea 'nete ea peptide e ikemiselitseng ho leka ho hloka melaoana e matla ea taolo ea boleng e netefatsang botšepehi ba sebopeho., bohloeki, le ho lokoloha ho litšila tse sitisang liteko.
Targeted Synthesis & Phetoho
Analytical RP-HPLC ► Netefatso ea Bohloeki (≥95%–98% Sebaka se Tlas'a Mokokotlo) E phahameng-Resolution ESI-MS ► Monoisotopic Mass & Phetoho Tiisetso Sehlopha 100 Ho sebetsa ka kamoreng ea bohloeki } Taolo ea Endotoxin (<0.5 EU/mg) bakeng sa Bioassays
1. Boima ba Boima ba Boipheliso bo Phahameng (HRMS/ESI-MS)
Sehlopha se seng le se seng se kopaneng se tlameha ho netefatsoa ka bongata ba monoisotopic ka Electrospray Ionization Mass Spectrometry. (ESI-MS) kapa Matrix-Assisted Laser Desorption/Ionization Nako-of-Flight (MALDI-TOF). Bakeng sa bakhethoa ba fetotsoeng ba nang le li-staples tsa hydrocarbon, cyclic disulfides, kapa biotin/fluorophore conjugates, Karohano ea MS kapa tlhahlobo ea boima bo phahameng e tiisa stoichiometry ea lik'hemik'hale e nepahetseng mme e thibela litlatsetso tse sa phethahalang tsa phetoho..
2. Analytical RP-HPLC Purity Profiles
Liteko tsa mantlha tse tlamang le lithuto tsa sebopeho li hloka lisebelisoa tse hloekileng haholo (≥ 95% kapa ≥ 98% bohloeki ka HPLC AUC ka 220 nm le 280 nm). Analytical RP-HPLC profiles Kpv e lokela ho bonts'a bohale, litlhoro tse lekanang ntle le tšilafalo ea mahetla a sephara e bonts'ang li-diastereomer, tatellano ya ho hlakolwa, kapa li-oligomers tse qhibilihang.
3. Ts'ebetso e Hlapang le Litlhaloso tse tlase tsa Endotoxin
Bakeng sa liteko tsa phetisetso ea mats'oao a thehiloeng liseleng kapa lithutong tsa pharmacokinetic tsa vivo, Litokisetso tsa peptide tse sebetsoang libakeng tse sa laoleheng tsa tšoaetso ea kotsi ka lipopolysaccharides tsa baktheria. (LPS/endotoxins). Li-endotoxins li etsa hore ho be le li-receptor tse sa khetheheng (TLR4) kenya tshebetsong, e lebisang ho chefo ea cellular le data ea bohata. Ho hlahisa li-peptide ka har'a Sehlopha 100 Libaka tse hloekileng tsa likamore tse hloekileng li netefatsa hore maemo a endotoxin a lula a le ka tlase ho meeli e thata ea biopharmaceutical. (<0.5 EU/mg).
Ho Potlakisa Peptide Lead Optimization: Moralo oa Bohato o Hlophisitsoeng Pele
Ka ho kopanya metrics ea moralo oa khomphutha o nang le liphetoho tse ikhethileng tsa lik'hemik'hale, lihlopha tsa lipatlisiso tsa biopharma li ka felisa potoloho e pheta-phetoang ea liteko le liphoso tse atisang ho thibela matšolo a ho sibolla peptide..
• Beha bakhethoa ka ΔG tlama le ho ikopanya le lintlha tse tlatselletsang tsa 'mapa. • Sefa khahlanong le sebaka sa hydrophobic, MOHLOMI, le tefiso ea letlooa. • Khetha li-tag tse qhibilihang tsa solubilizing bakeng sa ho otla ha hydrophobic haholo.
PEPTIDE E TSOANG PELE E KA HO ETSANG MOHATO OA MOSEBETSI OA MOSEBETSI 1: COMPUTER HIT TRIAGE MOHATO 2: HO SILICO LIABILITY MMAP • Hlalosa hore na ke mathateng a mang a se nang polar (>4 masalla). • Ho bolela esale pele ka ho kopana ha resin le likotsi tsa ho se qhibilihe ha metsi. MOHATO 3: TLHALOSO E REELENG YA PHETOHO YA Khemikhale • Kenyelletsa staples ya hydrocarbon (ke, ke+4) bakeng sa li-floppy α-helices. • Lileibole tsa boemo ba Biotin/FITC tse nang le li-spacers tse tenyetsehang tsa Ahx. MOHATO 4: SETSEBI TS'OANE & TIISETSO EA TLHOKOMELISO ea CoA • Etsa Fmoc-SPPS ka matrices a khethehileng a resin. • Netefatsa ka RP-HPLC (≥95%+), ESI-MS, le tlhahlobo ea endotoxin.
Ho fetolela lipina tsa sebele tse kang Peptide VB ho ea 'meleng, Lieta tse itokiselitseng liteko li hloka molekane oa motsoako ea khonang ho etsa liphetoho tse rarahaneng tsa lik'hemik'hale ka litekanyetso tse phahameng tsa bohloeki le taolo e hloekisitsoeng..
Ka sethala sa rona se khethehileng sa lipatlisiso le tlhahiso, tloaelo ea peptide synthesis le litšebeletso tse khethehileng tsa phetoho ho MOL Changes e fana ka lihlopha tsa biopharma tšehetso ea ho qetela-ho tloha ka tatellano ea pele le leano la ho fetola ho ea ho Sehlopha. 100 tlhahiso e nyopa, tloaelo solubilizing tag tlhomamiso, macrocyclization, le Setifikeiti sa Analysis sa HPLC/MS se felletseng (CoA) litokomane.
Ka ho hokahanya likhakanyo tsa khomphutha le motsoako oa lik'hemik'hale o hlophisitsoeng ho tloha letsatsing la pele, bafuputsi ba ka nts'etsapele ka kholiseho batho ba bona ba ts'episang haholo ba li-peptide ho hlahloba liteko kapele, ka botshepehi bo hodimo, le ka litšenyehelo tse fokolang haholo tsa ho pheta-pheta.
