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Using ELP Repeats as a Scaffold for De Novo Construction of Gadolinium-Binding Domains within Multifunctional Recombinant Proteins for Targeted Delivery of Gadolinium to Tumour Cells

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dc.contributor.authorPozdniakova, N. V.
dc.contributor.authorRyabaya, O. V.
dc.contributor.authorSemkina, A. S.
dc.contributor.authorShevelev, A. B.
dc.contributor.authorSkribitsky, V. A.
dc.contributor.authorСкрибицкий, Всеволод Андреевич
dc.date.accessioned2024-12-26T10:00:23Z
dc.date.available2024-12-26T10:00:23Z
dc.date.issued2022
dc.description.abstract© 2022 by the authors. Licensee MDPI, Basel, Switzerland.Three artificial proteins that bind the gadolinium ion (Gd3+) with tumour-specific ligands were de novo engineered and tested as candidate drugs for binary radiotherapy (BRT) and contrast agents for magnetic resonance imaging (MRI). Gd3+-binding modules were derived from calmodulin. They were joined with elastin-like polypeptide (ELP) repeats from human elastin to form the fourcentre Gd3+-binding domain (4MBS-domain) that further was combined with F3 peptide (a ligand of nucleolin, a tumour marker) to form the F3-W4 block. The F3-W4 block was taken alone (E2-13W4 protein), as two repeats (E1-W8) and as three repeats (E1-W12). Each protein was supplemented with three copies of the RGD motif (a ligand of integrin αvβ3) and green fluorescent protein (GFP). In contrast to Magnevist (a Gd-containing contrast agent), the proteins exhibited three to four times higher accumulation in U87MG glioma and A375 melanoma cell lines than in normal fibroblasts. The proteins remained for >24 h in tumours induced by Ca755 adenocarcinoma in C57BL/6 mice. They exhibited stability towards blood proteases and only accumulated in the liver and kidney. The technological advantages of using the engineered proteins as a basis for developing efficient and non-toxic agents for early diagnosis of tumours by MRI as well as part of BRT were demonstrated.
dc.identifier.citationUsing ELP Repeats as a Scaffold for De Novo Construction of Gadolinium-Binding Domains within Multifunctional Recombinant Proteins for Targeted Delivery of Gadolinium to Tumour Cells / Pozdniakova, N.V. [et al.] // International Journal of Molecular Sciences. - 2022. - 23. - № 6. - 10.3390/ijms23063297
dc.identifier.doi10.3390/ijms23063297
dc.identifier.urihttps://www.doi.org/10.3390/ijms23063297
dc.identifier.urihttps://www.scopus.com/record/display.uri?eid=2-s2.0-85126696131&origin=resultslist
dc.identifier.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000775541700001
dc.identifier.urihttps://openrepository.mephi.ru/handle/123456789/28885
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.titleUsing ELP Repeats as a Scaffold for De Novo Construction of Gadolinium-Binding Domains within Multifunctional Recombinant Proteins for Targeted Delivery of Gadolinium to Tumour Cells
dc.typeArticle
dspace.entity.typePublication
oaire.citation.issue6
oaire.citation.volume23
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relation.isAuthorOfPublication.latestForDiscovery102f6066-ce7f-4ef8-8188-76c5b237ebf1
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