Identification of dominant conformational epitopes from the whole structure of the proprotein convertase subtilisin/kexin type 9.
Biochem Biophys Res Commun
; 606: 55-60, 2022 05 28.
Article
em En
| MEDLINE
| ID: mdl-35339752
ABSTRACT
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of LDLR, has emerged as an important target for the treatment of hypercholesterolemic cardiovascular disease, and monoclonal antibodies alirocumab and evolocumab against it have been widely used in clinical practice. The vaccine research of PCSK9 is considered a promising option for the long-term treatment and prevention of cardiovascular disease, but progress has been slow. The selection of safe and effective epitopes is one of the key steps in vaccine development. In this study, we designed a phage display library of cascaded peptides for affinity screening with two antibody drugs, and found that the two peptides PC3 and PS6, which are adjacent to each other in protein spatial structure, both have superior binding activity to the screening antibodies. We performed in vitro recombination design on the dominant sequences, and obtained recombinant sequences that can respond to the dominant conformational epitope of PCSK9, which provides a meaningful reference for epitope selection in subsequent PCSK9 vaccine development.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças Cardiovasculares
/
Pró-Proteína Convertase 9
/
Epitopos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article