DNA Aptamer Binding Octapeptide Repeat Region of Cellular Prion Protein

Jing Sheng; Nan Zhang; Zhenhao Long; Xiangru Zhang; Shuang Zu; Xiangjun Liu; Dihua Shangguan

doi:10.1021/acs.analchem.3c04557

DNA Aptamer Binding Octapeptide Repeat Region of Cellular Prion Protein

Anal Chem. 2023 Dec 19;95(50):18595-18602. doi: 10.1021/acs.analchem.3c04557. Epub 2023 Dec 4.

Authors

Jing Sheng^{1

2}, Nan Zhang¹, Zhenhao Long^{1

2}, Xiangru Zhang^{1

2}, Shuang Zu^{3

4}, Xiangjun Liu^{1

2}, Dihua Shangguan^{1

2

3}

Affiliations

¹ Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Bio-systems, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
² School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
³ School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310013, China.
⁴ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

PMID: 38048047
DOI: 10.1021/acs.analchem.3c04557

Abstract

Cellular prion protein (PrP^C) is highly expressed in a variety of tumor cells and plays a crucial role in neurodegenerative diseases. Its N-terminal domain contains a conserved octapeptide (PHGGGWGQ) repeat sequence. The number of repeats has been correlated with the species as well as the development of associated diseases. Herein, PrP^C was identified to be the molecular target of a high-affinity DNA aptamer HA5-68 obtained by cell-SELEX. Aptamer HA5-68 was further optimized to two short sequences (HA5-40-1 and HA5-40-2), and its binding site to PrP^C was identified to be located in the loop-stem-loop region of the head of its secondary structure. HA5 series aptamers were demonstrated to bind the octapeptide repeat region of PrP^C, as well as the synthesized peptides containing different numbers of octapeptide repeats. The PrP^C expression on 42 cell lines was measured by using aptamer HA5-68 as a molecular probe. The clear understanding of the molecular structure and binding mechanism of this set of aptamers will provide information for the design of diagnostic methods and therapeutic drugs targeting PrP^C.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aptamers, Nucleotide* / chemistry
Binding Sites
Humans
Prion Diseases* / metabolism
Prion Proteins
Prions* / genetics
Protein Binding

Substances

Prion Proteins
Aptamers, Nucleotide
Prions