The design, synthesis and evaluation of affinity ligands for prion proteins.
Bifunctional affinity ligands based on a triazine scaffold were rationally designed to target prion protein and shown to bind recombinant prion protein with high affinity and selectivity. The ligands were capable of discriminating between prion protein glycoforms and monomeric and dimeric forms of the prion protein. The ligands also discriminate between conformational differences in the prion protein, resulting from point mutations in the prion protein gene. These results suggest that derived compounds could be used selectively to detect the disease-associated form of the prion protein, and as such, could provide diagnostic or therapeutic tools for prion diseases.
Soto Renou
Emma N
EN
University of Cambridge, Institute of Biotechnology, Tennis Court Road, Cambridge CB2 1QT, UK.
Gupta
Geeta
G
Young
Duncan S
DS
Dear
Denise V
DV
Lowe
Christopher R
CR
D000818:Animals; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012756:Sheep; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D011328:Prions; D014227:Triazines