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Prion‐Protein‐Specific Aptamer Reduces PrP Sc Formation
Author(s) -
Proske Daniela,
Gilch Sabine,
Wopfner Franziska,
Schätzl Hermann M.,
Winnacker ErnstL.,
Famulok Michael
Publication year - 2002
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/1439-7633(20020802)3:8<717::aid-cbic717>3.0.co;2-c
Subject(s) - gene isoform , prion protein , hamster , aptamer , biology , peptide , amino acid , nuclease , biochemistry , transmissible spongiform encephalopathy , rna , virology , microbiology and biotechnology , chemistry , scrapie , enzyme , gene , medicine , disease , pathology
The critical initial event in the pathophysiology of transmissible spongiform encephalopathies (TSEs) appears to be the conversion of the cellular prion protein (PrP C ) into the abnormal isoform PrP Sc . This isoform forms high‐molecular‐weight protease K (PK) resistant aggregates that accumulate in the central nervous system of affected individuals. We have selected nuclease‐resistant 2′‐amino‐2′‐deoxypyrimidine‐modified RNA aptamers which recognize a peptide comprising amino acid residues 90–129 of the human prion protein with high specificity. This domain of prion proteins is thought to be functionally important for the conversion of PrP C into its pathogenic isoform PrP Sc and is highly homologous among prion proteins of various species including mouse, hamster, and man. Consequently, aptamer DP7 binds to the full‐length human, mouse, and hamster prion protein. At low concentrations in the growth medium of persistently prion‐infected neuroblastoma cells, aptamer DP7 significantly reduced the relative proportion of de novo synthesized PK‐resistant PrP Sc within only 16 h. These findings may open the door towards a rational development of a new class of drugs for the therapy or prophylaxis of prion diseases.