LL-37

LL-37 kuyinto i-peptide ye-antimicrobial ukusuka i-cathelicidin umndeni. Igama ngokwalo libhekisela kuyo 37 ukwakheka kwe-amino acid kanye nokuqaliswa kwe-N-terminal kokubili i-leucine izinsalela. I-HCAP18, okuwukuphela kwelungu lomndeni we-cathelicidin womuntu, ihlukaniswa ngama-proteases abantu ukuze ikhulule lesi siqeshana se-LL-37 esisebenzayo..

Ukutholakala kwe-LL-37 kwaphawula ukuguqulwa okusemthethweni kocwaningo lwe-cathelicidin ukusuka ezilwaneni kuya kubantu.. Njengengxenye ebalulekile yamasosha omzimba azalwa nawo, I-LL-37 idlala indima ebalulekile ekuvikelweni komuntu kumagciwane.

Umsebenzi oyinhloko walokhu kuvikela umsebenzi oqondile we-antibacterial spectrum. I-amphipathic I-α-helical(I-Alpha helix) isakhiwo esinesibopho salo msebenzi siheha i-electrostatic kuma-membrane ebhaktheriya ashajwa kabi. Ukuphazamiseka okuqondile kobuqotho be-membrane kuholela ekulahlekelweni kwezakhi ze-intracellular; Ukufa okuphelele kwebhaktheriya kulandela. Ngokuphawulekayo, lo mshini awubangeli noma yiluphi uhlobo lokumelana.

Eminye imisebenzi engaphakathi emzimbeni nayo kuthiwa yenziwa yiyo – ukuphulukiswa kwesilonda, ukulungiswa kwezicubu, i-immunomodulation enamandla, i-endotoxin ukungathathi hlangothi, kanye nemiphumela elwa nomdlavuza kanye ne-anti-viral.

Ukulandelana

Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg-Glu-AV-Asn

Inombolo ye-CAS

154947-66-7

I-Molecular Formula

I-C205H340N60O53

Isisindo samangqamuzana

4493.34

LL-37 Ucwaningo oluhlobene

1.I-Broad-Spectrum Direct Antibacterial Activity

Isenzo esisheshayo nesiqondile se-bactericidal ngokumelene nezinhlobonhlobo eziningi ama-microorganisms kuwumsebenzi we-LL-37 obhalwe kahle kakhulu. I-Gram negative, positive, futhi ngisho nesikhunta amagciwane bonke babulawa ngempumelelo.

I-cationic, izici ze-amphipathic ze-peptide ziyisihluthulelo sale nqubo; izingxenye ezikhokhisiwe zibopha ngokuqondile kulwelwesi lwebhaktheriya. Ukuvuza kokuqukethwe kwamaselula kanye nokuwa kwamandla olwelwesi kuyimiphumela yokugcina yokuhlasela.

Ama-antibiotic endabuko asebenza ngendlela ehluke kakhulu (futhi ngokuvamile kuqondiswe ngqo) izindlela zokumelana; Imodi yokuhlasela ye-LL-37 ishesha futhi, kuze kube manje, akuhlotshaniswa nokuthuthukiswa okuphawulekayo kokumelana. Izifundo zemitholampilo yabantu zisekela ukuphepha nokusebenza kwe-LL-37 njenge-ejenti yokwelapha.

2.Umsebenzi onamandla we-Immunomodulatory

I-LL-37 inikeza imiphumela yayo ngokusekelwe ku-microenvironment yendawo ngaphakathi komzimba. Lapho kutholwa ukulimala kwezicubu noma izinguquko ze-pathological, I-LL-37 yenza kusebenze izici ezihlukahlukene zokulawula namaseli ukuze ahlanganiswe kulawa masayithi.

Ukuguqulwa kokukhishwa kwe-cytokine evuthayo kungenye yezindlela zayo eziyinhloko; ukusabela okweqile kwe-pro-inflammatory kulawulwa ngokukhethekile. Ukuphromotha i-dendritic cell(DC) ukuvuthwa nokulandelayo T cell ukwahlukanisa kungenye ingxenye esemqoka yale nqubo – emele ibhuloho elibalulekile phakathi kokugomela okuzelwe kanye nokuguquguqukayo.

3.Ukukhuthaza Ukuphulukiswa Kwezilonda kanye Nokulungiswa Kwezicubu

Ukuphulukiswa kwesilonda kwe-LL-37 namandla okulungisa izicubu kuxhumene ngqo nemisebenzi yayo yokuvikela umzimba, kanye nomsebenzi oqondile we-antimicrobial.

Ukwenza kusebenze izindlela ze-antimicrobial kubangela ama-keratinocyte, ama-fibroblasts, namaseli e-endothelial ukuze athuthele endaweni yenxeba; ukwanda kwamaseli kulandela njengoba umonakalo ulungiswa. I-Angiogenesis inikeza kokubili amandla nezakhi zokulethwa kwezicubu ezilimele.

4.Umsebenzi wokulwa nomdlavuza

Amaseli omdlavuza ngokuvamile ahlanganyela isici esivamile sokudalula amacala amabi phosphatidylserine kulwelwesi lwawo lwangaphandle (amaseli avamile anokwenziwa kwasendaweni kwangaphakathi kwalawa ama-phospholipids). Izindleko ezinhle ze-LL-37 zikhangwa ngakho.

I-apoptosis kanye nezindlela zokufa ze-necrotic ezifana nalezo ezisetshenziswa ngokumelene namagciwane ziyabe seziqalwa. Engaqondile i-anti-tumor imiphumela ngokuguqulwa kwamasosha omzimba nakho kunengxenye.

Ucwaningo lwe-preclinical lubonise ukuncipha okucacile kwamangqamuzana omdlavuza alashwa nge-LL-37; Ukwelapha ngomdlavuza kusetshenziswa i-LL-37 kuyindawo ethembisayo yocwaningo.

I-COA

I-HPLC

MS

(1) I-Chromek, M.; Slamova, Z.; Bergman, P.; Umkhandi wezinsimbi, L.; I-Podracka, L. u.; Ehrén, I.; Hökfelt, T.; Gudmundsson, G. H.; Gallo, R. L.; Agerberth, B.; et al. I-antimicrobial peptide cathelicidin ivikela umgudu womchamo ekuthelelekeni kwamagciwane ahlaselayo.. Umuthi Wemvelo 2006, 12 (6), 636-641. I-DOI: 10.1038/nm1407.

(2) Umlandeli, D.; Coughlin, L. A.; I-Neubauer, M. M.; UKim, J.; UKim, M. S.; Zhan, X.; Simms-Waldrip, T. R.; Xie, Y.; I-Hooper, L. V.; Koh, A. Y. Ukwenziwa kusebenze kwe-HIF-1α ne-LL-37 ngamabhaktheriya e-commensal kuvimbela i-Candida albicans colonization. Umuthi Wemvelo 2015, 21 (7), 808-814. I-DOI: 10.1038/nm.3871.

(3) U-Chen, X.; Deng, S.; Wang, W.; I-Castiglione, S.; Duan, Z.; IsiLuo, L.; Cianci, F.; Zhang, X.; Xu, J.; Li, H.; et al. I-peptide ye-antimicrobial yabantu i-LL-37 inomthelela ekuqhubekeleni phambili kwesifo i-Alzheimer's. I-Molecular Psychiatry 2022, 27 (11), 4790-4799. I-DOI: 10.1038/s41380-022-01790-6.

(4) Yikuphi, X.; Guo, J.-L.; Yena, J.; Futhi, R.-J.; U-Liu, P.-P.; Zhang, Z.-R.; Wang, A.-M.; Zhang, J. I-Chitosan hydrogel ehlanganiswe ne-LL-37 peptide ikhuthaza ukuphulukiswa kokulimala kwezicubu ezijulile kumodeli yegundane.. Ucwaningo Lwezempilo Lwezempi 2020, 7 (1). I-DOI: 10.1186/s40779-020-00249-5.

(5) Zhou, Q.; Ipani, L.-L.; Xue, R.; Ku, G.; Duan, Y.; Bayi, Y.; Shi, C.; Ren, Z.; Wu, C.; Li, G.; et al. Amazinga e-anti-microbial peptide LL-37/CRAMP ahlotshaniswa nokuhluleka kwenhliziyo okunamandla futhi anganciphisa ukungasebenzi kahle kwenhliziyo kumamodeli amaningi angaphambi komtholampilo wokuhluleka kwenhliziyo.. I-Theranostics 2020, 10 (14), 6167-6181. I-DOI: 10.7150/cha. 46225.

(6) Ren, S. X.; Cheng, A. S. L.; Kuya, K. F.; Tong, J. H. M.; Li, M. S.; Shen, J.; Wong, C. C. M.; Zhang, L.; Chan, R. L. Y.; Wang, X. J.; et al. I-Peptide Yokuvikela Amasosha omzimba I-LL-37 Isebenza I-Caspase-Independent Apoptosis futhi Icindezela Umdlavuza Wamathumbu. Ucwaningo lweCancer 2012, 72 (24), 6512-6523. I-DOI: 10.1158/0008-5472.Can-12-2359.

ukucaciswa	10mg, 2mg

Imikhiqizo

Izindaba

LL-37