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1kits (Ebipipa 10) .
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▎ Enzimba ya LL-37
Ensibuko: PubChem |
Omutendera: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES Ensengekera ya molekyu: C 205H 340N 60O53 Obuzito bwa molekyu: 4493 g/mol Ennamba ya CAS: 154947-66-7 Ekitabo kya PubChem CID: 16198951 Ebigambo ebikwatagana: Cathelicidin;ropocamptide |
▎ LL-37 Okunoonyereza
Ensibuko y’okunoonyereza eya LL-37 eri etya?
LL-37 yasooka kuzuulibwa nga kiraasi y’ebintu ebitono ebiyitibwa cationic small peptide substances mu pupae z’ensowera ya silkworm Samia cynthia ricini nga yakolebwa munnasayansi Omusweden Boman HG mu 1980. LL-37 ye C-terminal peptide (CAMP, hCAP18) eya human cathelicidin antibacterial peptide, eyinza okwongera okuziyiza microbial okulumba era akola emirimu emikulu egy’omubiri mu chemotaxis, okutumbula okuggalawo ebiwundu, n’okuzimba emisuwa (Chen X, 2018). Peptides ezitta obuwuka zisangibwa nnyo mu bisolo, ebimera, n’obuwuka obutonotono, era kitundu kikulu nnyo mu buziyiza obuzaaliranwa obw’ebiramu ebirina omugongo. Nga puloteyina ey’ekyama, LL-37 esangibwa nnyo mu bitundu by’omubiri n’ebitundu by’omubiri ebingi eby’omubiri gw’omuntu. Obutoffaali obw’enjawulo, omuli obutoffaali obuyitibwa epithelial cells, keratinocytes, mast cells, neutrophils, macrophages, ne monocytes, busobola okubufulumya. Eddagala ly'ekika kino erisinga lirimu 'amino acid residues' 37 - 39 era lirina 0 cysteine. Olw'obuziba obw'amaanyi ku kifo kya N-terminal ekya peptide eritta obuwuka, esobola okukola 'amphhiphilic helical structure' ennywevu. Peptide etta obuwuka LL-37 nayo erina 'ensengekera ya α-helical eya amphiphilic'. Olw’omulimu gwayo ogw’okutta obuwuka obuleeta endwadde, etuumiddwa erinnya lya peptide eritta obuwuka. '37' mu linnya LL-37 eyinza okuba nga yeekuusa ku muwendo gw'ebisigadde byayo ebya amino asidi. Mu kiseera kye kimu, era kimanyiddwa nga cathelicidin ne ropocamptide.
Enkola ya LL-37 ekola ku bakitiriya ezigumira eddagala eritta obuwuka eri etya?
Okutabangula oluwuzi lw’obutoffaali bwa bakitiriya:
LL-37 esobola okuyingiza mu luwuzi lw’obutoffaali bwa bakitiriya naddala ng’erina ekikolwa eky’okusaanyaawo oluwuzi lw’obutoffaali olulimu phosphatidylglycerol (DPPG). Kijja kutaataaganya ensengekera y’oluwuzi lw’obutoffaali bwa bakitiriya, bwe kityo kikole ekikolwa eky’okutta obuwuka [1] . Okugeza, okunoonyereza kuzudde nti LL-37 esobola okuyingira mu luwuzi lw’obutoffaali bwa bakitiriya zombi eza Gram-positive ne Gram-negative, ekivaako okweyongera kw’okuyita kw’oluwuzi lw’obutoffaali, okukulukuta kw’ebirimu mu butoffaali, n’okukkakkana nga bakitiriya n’efa.
Enkola y’okulwanyisa obuwuka mu ngeri empanvu:
LL-37 erina obusobozi bw’okulwanyisa obuwuka ku bakitiriya ez’enjawulo ezigumira eddagala. Kiyinza okukola ku bakitiriya abalina Gram-positive (nga Staphylococcus aureus, Streptococcus, Enterococcus, n’ebirala), obuwuka obuyitibwa Gram-negative bacteria (nga Pseudomonas aeruginosa, Escherichia coli, Salmonella, n’ebirala), n’obuwuka obulala obuleeta endwadde (nga Mycoplasma, Ureaplasma, Mycobacterium, n’ebirala) [2] . Omulimu guno ogw’okulwanyisa obuwuka ogw’enjawulo gufuula LL-37 okuba n’omugaso oguyinza okukozesebwa mu kulwanyisa ebika bya bakitiriya eby’enjawulo ebigumira eddagala.
Okusaanyaawo biofilm ekoleddwa:
Bacterial biofilm y’emu ku nsonga enkulu ezireetera obuwuka obuleeta endwadde okuziyiza eddagala. Peptide etta obuwuka LL-37 esobola okusaanyaawo biofilm ekoleddwa, bwe kityo ne kikendeeza ku buziyiza bw’eddagala bwa bakitiriya. Okugeza, mu bulwadde bw’ennyondo ez’ekinnansi (PJI) oluvannyuma lw’okukyusa ekiwanga mu ngeri ey’ekikugu, okuziyiza eddagala eri obuwuka obuleeta endwadde obuva ku biofilm ya bakitiriya kifuula obujjanjabi okukaluba. Naye LL-37 esobola okukola omulimu omulungi ogw’okulwanyisa obuwuka n’okuziyiza obuwuka ng’eziyiza okutondebwa kw’ekiwuka ekiramu n’okusaanyaawo ekiwujjo ekikoleddwa.
Okwongera ku mirimu gy’eddagala eritta obuwuka:
Okunoonyereza kulaga nti LL-37 erina ekikolwa eky’okukwatagana n’eddagala erimu eritta obuwuka. Okugeza, bwe ekozesebwa nga egattibwa wamu ne amoxicillin clavulanic acid (AMC), LL-37 esobola okutumbula ennyo emirimu gya AMC egy’okulwanyisa obuwuka.
Ensibuko:PubMed [6] .
Biki ebisaba LL-37?
Okutumbula okuddamu okukola amagumba:
Okunoonyereza okumu kulaga nti eddagala eritta obuwuka erya peptide LL-37 lirina akakwate akalungi ku kuzzaawo amagumba. Okunoonyereza okumu kulaga nti obutoffaali obusibuka mu masavu g’omuntu (hADSCs) bwakuzibwa n’obungi bwa LL-37 obw’enjawulo, era kyazuulibwa nti obungi bwa LL-37 bwalina kye bwakola ku busobozi bw’amagumba bwa hADSCs, ne butuuka ku ntikko ku 4μg/ml. Okugatta ku ekyo, PSeD/hADSCs/LL-37 combination scaffold yalaga omutindo gw’amagumba ogw’oku ntikko okusinga PSeD/hADSCs, PSeD, ne control group scaffolds mu rat calvarial defect model, ekiraga obusobozi obw’amaanyi mu kuzzaawo amagumba mu bujjanjabi.
Enkola y’okulwanyisa obuwuka:
Okuziyiza obuwuka obuleeta endwadde eziwera:
Okunoonyereza okumu kwakozesa enkola ya micro-double dilution okuzuula ekipimo ekitono ekiziyiza (MIC) eky’ekirungo ekiziyiza obuwuka LL-37 ku Escherichia coli, Salmonella, ne Staphylococcus aureus. Ebivuddemu biraga nti LL-37 yalina diguli ez’enjawulo ez’ebikolwa eby’okuziyiza ku bakitiriya zino essatu ezireeta endwadde, ng’obuzito obutono obw’okuziyiza bwali 3.12, 1.56, ne 0.78μg/mL, okusinziira ku. Okugezesa okutebenkera kw’ebbugumu kwalaga nti ekirungo ekiziyiza obuwuka obuyitibwa recombinant antibacterial peptide ekyalina omulimu omulungi ku bbugumu erya waggulu. Ebivudde mu kukebera okutebenkera kwa asidi-base byalaga nti LL-37 yalina emirimu egimu ku pH okuva ku 2.0 okutuuka ku 12.0, ng’emirimu egisinga obulungi ku pH ya 5.0 okutuuka ku 6.0, ne -20°C ye mbeera esinga obulungi ey’okutereka okumala ebbanga eddene [3]..
Ebikosa obuwuka obuziyiza obuwuka:
Abantu abamu baanoonyereza ku bulung’amu bw’eddagala eritta obuwuka erya peptide LL-37 ne silver nanoparticles (AgNPs) ku Staphylococcus aureus (S. aureus), obuwuka obutonotono obutera okusangibwa mu yinfekisoni ezeekuusa ku biofilm. Ebivuddemu biraga nti LL-37 ye yali eddagala erisinga okukola obulungi eritta obuwuka, nga likendedde mu muwendo gw’amakoloni okusukka logaritmu 4. Okwawukana ku ekyo, ebiva mu nanoparticles za ffeeza n’eddagala eritta obuwuka erya bulijjo byali bibi nnyo, nga omuwendo gw’amakolooni gwakendeera wansi wa logarithm emu. Obujjanjabi obw’okugatta eddagala eritta obuwuka ne rifampicin bwayongera nnyo ku kukendeera kwa logarithmic kwa AgNPs ne gentamicin, naye nga bukyali wansi nnyo okusinga obwa LL-37 eyakozesebwa yokka [4]..
Okukozesa mu bulwadde bw’amawuggwe:
Okunoonyereza kulaga nti Pseudomonas aeruginosa (PA) efuuse okusoomoozebwa okw’amangu eri obulwadde bw’amawuggwe n’okulumwa amawuggwe. LL37 peptide kirungo ekikola obulungi ekitta obuwuka ku bika bya PA, naye okukozesebwa kwayo kutono olw’okulongoosebwa kwayo okw’amangu mu vivo, ensonga z’obukuumi bw’ebiramu, n’obutabeera bulungi mu biramu. Nolwekyo, enkola y’okutuusa nanodrug eyesigamiziddwa ku albumin ekendeeza ku buwulize ekoleddwa okulongoosa omulimu gwa LL37 ku PA mu vivo nga ekola intermolecular disulfide bonds. Cationic LL37 esobola bulungi okusibwa okuyita mu nkolagana y’amasannyalaze okukola ekikolwa ekirongooseddwa eky’okulwanyisa obuwuka. LL37 peptide yalaga okufuluma okutambula okumala essaawa ezisukka mu 48 okuva mu LL37 peptide nanoparticles (LL37 PNP), era ekikolwa eky’okulwanyisa obuwuka ekigaziyiziddwa kyazuulibwa n’okweyongera kw’obudde bw’okufumbiza. Mu nkola y’ebibe ey’obulwadde bw’amawuggwe obwa PA obw’amangu, LL37 PNP yakendeeza nnyo ku kwolesebwa kwa TNF-α ne IL-1β era n’ekendeeza ku buvune bw’amawuggwe. Kiraga nti LL37 PNP esobola okulongoosa obulungi obulwadde bw’amawuggwe bwa PA n’okuddamu kw’okuzimba okuddirira okusinga peptide ya LL37 ey’obwereere [3]..
Okukola omulimu gw’okulwanyisa obuwuka obuyitibwa platelets:
Okunoonyereza kulaga nti ekirungo ekiziyiza obuwuka ekiyitibwa peptide LL-37 kisobola okukola emirimu gy’okulwanyisa obuwuka mu platelets z’omuntu. Oluvannyuma lw’obutoffaali obukola omusaayi okujjanjabwa ne LL-37, okwolesebwa okw’okungulu kw’ebikwata okutegeera obuwuka obutonotono (Toll-like receptors (TLRs) 2 ne -4, CD32, CD206, Dectin-1, CD35, LOX-1, CD41, CD62P, ne αIIbβ3 integrin) ne molekyu ezikwatagana n’okwanjula antigen eri T lymphocytes (CD80, CD86, ne HLA-ABC) zeeyongera, era molekyo ezitta obuwuka zifulumizibwa: puloteyina etta obuwuka/eyongera okuyita mu mazzi (BPI), azurocidin, human neutrophil peptide (HNP)-1, ne myeloperoxidase. Era zivvuunula azurocidin ne zongera okusiba ku Escherichia coli, Staphylococcus aureus, ne Candida albicans. Okugatta ku ekyo, amazzi aga waggulu ku platelets ezijjanjabiddwa ne LL-37 gasobola okuziyiza okukula kwa Escherichia coli, oba platelets zisobola okukozesa LL-37 yazo okuziyiza okukula kw’obuwuka obutonotono [5]..
Okukozesebwa mu nkola z’okutuusa eddagala
Okunoonyereza kwogera nti antibacterial peptides (AMPs) kiraasi empya eya biomolecules ezirina eby’obugagga ebiziyiza obuwuka mu ngeri egazi era zisikiriza okufaayo olw’okweyongera amangu mu kuziyiza eddagala [6] . LL37 ye peptide yokka evudde mu cathelicidin ekola antibacterial peptide esangibwa mu bantu. Nga tulina okunoonyereza okw’obwegendereza, LL37 eraga emirimu egy’enjawulo egy’ebiramu, omuli okulungamya enkola y’okuzimba, okuziyiza obutoffaali obuziyiza endwadde, okutumbula okuwona kw’ebiwundu, n’okukola amagumba, ebikubirizza okukozesa eby’enjawulo mu bujjanjabi. Naye, enkyusa y’obujjanjabi eya LL37 ekoma olw’obuwulize bwayo eri okuvunda kwa protease, obutwa obuyinza, obutabeera bulungi mu biramu, n’ebirala Enkola ez’enjawulo ez’okutuusa, omuli ebyuma nanoparticles, polymer materials, n’enkola ezesigamiziddwa ku lipid, zitongozeddwa okutuuka ku kukozesebwa mu bujjanjabi.
Mu kumaliriza, nga multifunctional bioactive peptide, LL-37 eraga obusobozi bungi mu kukozesebwa mu bujjanjabi. Mu nsonga z’okutumbula okuddamu okukola kw’amagumba, okuyita mu bikolwa ebikwatagana eby’enkola eziwera nga okutumbula okwawukana n’okukola kw’amagumba, ebikolwa ebiziyiza obuwuka, okukyusakyusa obusimu obuziyiza endwadde, n’okutumbula okuzimba emisuwa, kireese essuubi eppya ery’okuddaabiriza obuvune bw’amagumba. Bwe tukolagana ne bakitiriya ezigumira eddagala, nga zisaanyaawo butereevu oluwuzi lw’obutoffaali, nga ziziyiza okutondebwa kw’ebiramu ebiyitibwa biofilms, era nga zikwatagana n’eddagala eritta obuwuka, kisuubirwa okufuuka eky’okulwanyisa eky’amaanyi okugonjoola ekizibu kya bakitiriya ezigumira eddagala. Mu nkola z’okutuusa eddagala, nga tukola enteekateeka n’okulongoosa enkola za peptide ezitta obuwuka, nga tuzimba enkola eziwera ez’okutuusa eddagala, n’okunoonyereza ku nkozesa y’eddagala okugatta, ekikolwa kyayo eky’obujjanjabi mu bujjanjabi kiyinza okwongera okunywezebwa. Mu bufunze, LL-37 erina obusobozi mu bintu ebingi eby’okukozesa mu bujjanjabi, omuli okutumbula okuddamu okukola amagumba, ebikolwa ebiziyiza obuwuka, okukola omulimu gw’okulwanyisa obuwuka obuyitibwa platelets, n’okukozesebwa mu nkola z’okutuusa eddagala.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Francisco J. Sanchez-Pena munoonyereza mu Universidad Autonoma Benito Juarez de Oaxaca (Yunivasite y’e Oaxaca eyeetongodde Benito Juarez). Yunivasite eno eyatandikibwawo mu 1827, ttendekero lya gavumenti ery’amaanyi mu Oaxaca, Mexico, erikola pulogulaamu ez’enjawulo ez’ebyenjigiriza mu bintu nga ssaayansi w’obutonde, yinginiya, eby’obuntubulamu, ne ssaayansi w’embeera z’abantu.
Okunoonyereza kwa Francisco J. Sanchez-Pena kwesigamye ku Biochemistry & Molecular Biology, Microbiology, ne Chemistry. Emisomo gino gizingiramu okunoonyereza ku nkola za kemiko mu biramu, ensengekera za molekyu n’emirimu gyazo, engeri z’obuwuka obutonotono n’enkolagana yazo n’obutonde, awamu n’obutonde, eby’obugagga, n’amateeka g’enkyukakyuka y’ebintu eby’eddagala. Okunoonyereza mu bintu bino kulina enkizo nnene mu by’obusawo, eby’obulimi, ssaayansi w’obutonde bw’ensi, n’ebirala. Francisco J. Sanchez-Pena awandiikiddwa mu kiwandiiko ekijuliziddwa [5].
