Conformation-reconstructed multivalent antibody mimic for amplified mitigation of human islet amyloid polypeptide amyloidogenesis

Autor:	Liyuan Zhao, Sheng Wang, Qigang Hu, Haibo Jia, Yanru Xin, Liang Luo, Fanling Meng
Rok vydání:	2022
Předmět:	Amyloid Islets of Langerhans endocrine system Diabetes Mellitus Type 2 Humans Metal Nanoparticles General Materials Science Gold Islet Amyloid Polypeptide
Zdroj:	Nanoscale. 14:2802-2815
ISSN:	2040-3372 2040-3364
DOI:	10.1039/d1nr08090c
Popis:	The misfolding and aggregation of human islet amyloid polypeptide (IAPP) into β-sheet-enriched amyloid fibrils is linked to type 2 diabetes. Antibodies are potent inhibitors of IAPP amyloidogenesis, but their preparation is usually complicated and expensive. Here we have created a multivalent antibody mimic SPEPS@Au through conformational engineering of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs). By immobilizing both terminals of an IAPP-recognizing CDR loop (PEP) on the surface of AuNPs, the active conformation of PEP can simply recur on the gold-based antibody mimic, significantly enhancing the binding affinity between PEP and IAPP. SPEPS@Au mitigated amyloidogenesis of IAPP at low sub-stoichiometric concentrations, even after IAPP started aggregating, and dramatically reduced the amyloidogenesis-induced toxicity and ROS production both
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88e3be0036892e88f07293f38efc1e03 https://doi.org/10.1039/d1nr08090c Zobrazit plný text záznamu