title: Palladium complexes affect the aggregation of human prion protein PrP106-126.
abstract: Many neurodegenerative disorders are induced by protein conformational change. Prion diseases are characterized by protein conformational conversion from a normal cellular form (PrP(C)) to an abnormal scrapie isoform (PrP(Sc)). PrP106-126 is an accepted model for studying the characteristics of PrP(Sc) because they share many biological and physiochemical properties. To understand how metal complexes affect the property of the prion peptide, the present work investigated interactions between Pd complexes and PrP106-126 based on our previous research using Pt and Au complexes to target the peptide. The selected compounds (Pd(phen)Cl(2), Pd(bipy)Cl(2), and Pd(en)Cl(2)) showed strong binding affinity to PrP106-126 and affected the conformation and aggregation of this active peptide in a different binding mode. Our results indicate that it may be the metal ligand-induced spatial effect rather the binding affinity that contributes to better inhibition on peptide aggregation. This finding would prove valuable in helping design and develop novel metallodrugs against prion diseases.
authors.affiliation: Department of Chemistry, Renmin University of China, Beijing 100872, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Bingbing
authors.initials: B
authors.lastname: Zhang
authors.forename: Xuesong
authors.initials: X
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.forename: Weihong
authors.initials: W
authors.lastname: Du
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009447:Neuroblastoma / Q000188:drug therapy; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry* / Q000378:metabolism; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D017096:Prion Diseases / Q000188:drug therapy / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D020033:Protein Isoforms / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D009942:Organometallic Compounds; D018620:PrPSc Proteins; D011328:Prions; D020033:Protein Isoforms; D010165:Palladium