Affinity capillary electrophoresis is a powerful tool to identify transthyretin binding drugs for potential therapeutic use in amyloidosis.
In this work we used affinity capillary electrophoresis (ACE) to investigate the extent of interaction between a pool of drugs and wild-type transthyretin. After qualitative preliminary screening, attention was focused on the most promising molecules, flufenamic acid and flurbiprofen, which underwent a further stage of investigation, the determination of the binding constants, and, when possible, the assessment of the number of binding sites by ACE, frontal analysis (FA) capillary electrophoresis (CE) and parallel ultrafiltration (UF) experiments. Furthermore, our data demonstrate that FA CE is a suitable technique for identifying fibril ligands. This represents a novel CE application of pharmaceutical interest.
De Lorenzi
E
E
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pavia, Italy. ersilia@chifar.unipv.it
Galbusera
C
C
Bellotti
V
V
Mangione
P
P
Massolini
G
G
Tabolotti
E
E
Andreola
A
A
Caccialanza
G
G
D000686:Amyloidosis / Q000097:blood / Q000188:drug therapy; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D001665:Binding Sites; D019075:Electrophoresis, Capillary / Q000379:methods; D005439:Flufenamic Acid / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D005480:Flurbiprofen / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D014462:Ultrafiltration / Q000379:methods
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011228:Prealbumin; D005480:Flurbiprofen; D005439:Flufenamic Acid