Amyloidogenicity and aggregate cytotoxicity of human glucagon-like peptide-1 (hGLP-1).
The potential of human glucagon-like peptide-1 (hGLP-1) as a therapeutic agent is limited by its high aggregation propensity. We show that hGLP-1 forms amyloid-like structures that are preceded by cytotoxic aggregates, suggesting that aggregation of biopharmaceuticals could present a cytotoxic risk to patients besides the reported increased risk in immunogenicity.
Poon
S
S
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK.
Birkett
N R
NR
Fowler
S B
SB
Luisi
B F
BF
Dobson
C M
CM
Zurdo
J
J
D000682:Amyloid / Q000378:metabolism* / Q000633:toxicity* / Q000648:ultrastructure; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D007700:Kinetics; D051379:Mice; D046529:Microscopy, Electron, Transmission; D041681:NIH 3T3 Cells; D014961:X-Ray Diffraction
D000682:Amyloid; D052216:Glucagon-Like Peptide 1