Iimpawu zesakhiwo kunye nokuhlelwa kweepeptide ze-transmembrane

Kukho iintlobo ezininzi ze-peptides ze-transmembrane, kwaye ukuhlelwa kwazo kusekelwe kwiipropati zomzimba kunye neekhemikhali, imithombo, iindlela zokungena, kunye nokusetyenziswa kwe-biomedical.Ngokweempawu zabo zomzimba kunye neekhemikhali, i-membrane engena kwi-peptides inokwahlulwa ibe ziindidi ezintathu: i-cationic, i-amphiphilic kunye ne-hydrophobic.I-Cationic kunye ne-amphiphilic membrane engena kwi-peptides yenza i-85%, ngelixa i-hydrophobic membrane engena kwi-peptides i-15% kuphela.

1. Inwebu yeCationic peptide engena

Iipeptide zeCationic transmembrane zenziwe ngeepeptide ezimfutshane ezityebileyo kwi-arginine, i-lysine, kunye ne-histidine, njenge-TAT, i-Penetratin, i-Polyarginine, i-P22N, i-DPV3 kunye ne-DPV6.Phakathi kwazo, i-arginine iqulethe i-guanidine, enokuthi i-hydrogen bond kunye namaqela e-phosphoric acid ehlawuliswa kakubi kwi-membrane yeseli kwaye idibanise i-peptides ye-transmembrane kwi-membrane phantsi kwemeko yexabiso le-PH ye-physiological.Izifundo ze-oligarginine (ukusuka kwi-3 R ukuya kwi-12 R) zibonise ukuba ikhono lokungena kwi-membrane liphunyezwe kuphela xa inani le-arginine liphantsi njenge-8, kwaye i-membrane yokungena kwi-membrane yanda ngokuthe ngcembe ngokunyuka kwenani le-arginine.I-Lysine, nangona i-cationic njenge-arginine, ayinayo i-guanidine, ngoko xa ikhona yodwa, ukusebenza kwayo kwe-membrane yokungena ayiphezulu kakhulu.UFutaki et al.(2001) yafumanisa ukuba isiphumo esihle sokungena kwi-membrane sinokufezekiswa kuphela xa i-cationic cell membrane ingena kwi-peptide iqulethe ubuncinane i-amino acids ehlawulweyo eyi-8.Nangona iintsalela ze-amino acid ezihlawulwe ngokufanelekileyo ziyimfuneko kwiipeptide ezingenayo ukungena kwi-membrane, ezinye i-amino acids zibaluleke ngokulinganayo, njengokuba i-W14 iguqulela kwi-F, ukungena kwe-Penetratin kulahleka.

Udidi olukhethekileyo lwe-cationic transmembrane peptides yi-nuclear localization sequences (NLSs), equlathe iipeptides ezimfutshane ezityebileyo kwi-arginine, i-lysine kunye ne-proline kwaye zinokuthuthelwa kwi-nucleus nge-nucleus pore complex.Ii-NLS zinokuphinda zohlulwe zibe luhlobo olunye kunye nokuchwetheza kabini, okubandakanya iqoqo elinye kunye nesibini se-amino acid esisiseko, ngokulandelelanayo.Umzekelo, i-PKKKRKV evela kwi-simian virus 40(SV40) yi-NLS yokuchwetheza enye, ngelixa iprotheni yenyukliya ichwetheza kabini i-NLS.I-KRPAATKKAGQAKKKL lulandelelwano olufutshane olunokuthi ludlale indima kwi-membrane ye-membrane.Ngenxa yokuba uninzi lwee-NLS zinamanani entlawulo angaphantsi kwe-8, ii-NLSs aziyiyo i-transmembrane peptides esebenzayo, kodwa zinokusebenza ngokusebenzayo ii-transmembrane peptides xa zidityaniswe ngokudibeneyo nolandelelwano lwe-hydrophobic peptide ukwenza i-amphiphilic transmembrane peptides.

ngokwesakhiwo-2

2. I-Amphiphilic transmembrane peptide

I-amphiphilic transmembrane peptides iqukethe i-hydrophilic kunye ne-hydrophobic domains, enokuthi ihlulwe ibe yi-amphiphilic yokuqala, i-secondary α-helical amphiphilic, i-β-folding amphiphilic kunye ne-prolin-enriched amphiphilic.

Uhlobo oluphambili lwe-amphiphilic ukunxiba i-membrane peptides kwiindidi ezimbini, udidi kunye ne-NLSs edityaniswe ngokudibeneyo ngolandelelwano lwe-hydrophobic peptide, njengeMPG (GLAFLGFLGAAGSTMGAWSQPKKKRKV) kunye ne-Pep - 1 (KETWWETWWTEWSQPKKRKV), Zombini zisekwe kumqondiso wenyukliya we-PKK4phobic ye-PKK4phorkV, i-domain ye-MPG inxulumene nokulandelelana kwe-fusion ye-HIV glycoprotein 41 (GALFLGFLGAAGSTMG A), kunye ne-hydrophobic domain ye-Pep-1 inxulumene ne-tryptophan rich cluster ene-high membrane affinity (KETWWET WWTEW).Nangona kunjalo, imimandla ye-hydrophobic yazo zombini idityaniswe nophawu lwenyukliya lwe-PKKKRKV nge-WSQP.Enye iklasi ye-primary amphiphilic transmembrane peptides yahlukaniswa kwiiprotheni zendalo, ezifana ne-pVEC, i-ARF (1-22) kunye ne-BPrPr (1-28).

I-alpha-helical amphiphilic transmembrane peptides yesibini ibophelela kwi-membrane nge-α-helices, kunye ne-hydrophilic kunye ne-hydrophobic amino acid esele ifumaneka kwiindawo ezahlukeneyo zesakhiwo se-helical, njenge-MAP (KLALKLALK ALKAALKLA).Kuhlobo olusongayo lwe-beta peptide yohlobo lwe-amphiphilic wear inwebu, ukukwazi kwayo ukwenza i-beta pleated sheet ibalulekile kwisakhono sayo sokungena kwinwebu, njengakwi-VT5 (DPKGDPKGVTVTVTVTVTVTGKGDPKPD) kwinkqubo yophando lokungena kwenwebu, kusetyenziswa uhlobo D. - i-amino acid yokuguqulwa kwe-analogues ayikwazanga ukwenza isiqwenga esisongekileyo se-beta, ukukwazi ukungena kwinwebu kubi kakhulu.Kwi-proline-enriched amphiphilic transmembrane peptides, i-polyproline II (PPII) yenziwa ngokulula emanzini acocekileyo xa iproline ityetyiswe kakhulu kwisakhiwo se-polypeptide.I-PPII yi-helix yesandla sasekhohlo kunye neentsalela ze-amino acid ezi-3.0 ngokujika, ngokuchasene nesakhiwo esilungileyo se-alpha-helix esine-3.6 intsalela ye-amino acid ngokujika.I-proline-enriched amphiphilic transmembrane peptides iquka i-bovine antimicrobial peptide 7(Bac7), synthetic polypeptide (PPR)n(n ingaba yi-3, 4, 5 kunye ne-6), njl.

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3. Hydrophobic inwebu engena peptide

Iipeptide ze-Hydrophobic transmembrane ziqulethe kuphela iintsalela ze-amino acid ezingekho-polar, kunye nentlawulo engaphantsi kwe-20% yentlawulo epheleleyo yokulandelelana kwe-amino acid, okanye iqulethe i-hydrophobic moieties okanye amaqela ekhemikhali ayimfuneko kwi-transmembrane.Nangona ezi peptides zeselula ze-transmembrane zihlala zingahoywa, zikhona, njenge-fibroblast growth factor (K-FGF) kunye ne-fibroblast growth factor 12 (F-GF12) esuka kwi-Kaposi's sarcoma.


Ixesha lokuposa: Mar-19-2023