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Modulation of Prion by Small Molecules: From Monovalent to Bivalent and Multivalent Ligands

[ Vol. 13 , Issue. 19 ]

Author(s):

Matteo Staderini, Giuseppe Legname, Maria Laura Bolognesi and J. Carlos Menéndez   Pages 2491 - 2503 ( 13 )

Abstract:


Prion diseases are fatal neurodegenerative disorders that affect humans and animals and for which no pharmacological treatment is available. Compounds consisting of two identical moieties joined via an appropriate spacer (i.e. bivalent compounds) have turned out to be effective tools to prevent prion fibril formation and exhibit an improved biological profile with regard to the corresponding monovalent derivatives. In this review we discuss the importance of the bivalent strategy as a viable approach to design new chemical entities to combat prion diseases.

Keywords:

Prion protein, protein misfolding diseases, neurodegenerative diseases, protein-protein interaction, bifunctional ligands, molecular tweezers, palindromic compounds.

Affiliation:

Departamento de Química Orgánica y Farmacéutica, Universidad Complutense, 28040 Madrid, Spain.



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