Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 28, Issue 18, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2020.115676
Keywords
Amyloid beta-protein; beta-Sheet breaker peptide; beta-Strand mimetics; Conformation fixation; Conformation analysis
Funding
- Sugiyama Houkoukai
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Aggregation of 42-residue amyloid beta-protein (A beta 42) can be prevented by beta-sheet breaker peptides (BSBps) homologous to LVFFA residues, which are included in a beta-sheet region of A beta 42 aggregates. To enhance the affinity of BSBps to the A beta 42 aggregates, we designed and synthesized beta-strand-fixed peptides (BSFps) whose side chains were cross-linked by ring closing metathesis. Conformation analysis verified that the designed peptides could be fixed in beta-strand conformation. Among the synthesized pentapeptides, 1 and 12, whose side chains of 2nd and 4th residues were cross-linked, significantly inhibited the aggregation of A beta 42. This suggested that beta-strand-fixation of BSBps could enhance their inhibitory activity against the A beta 42 aggregation. However, pentapeptides 1 and 12 had little effect on morphology of A beta 42 aggregates (fibrils) and neurotoxicity of A beta 42 against SH-SY5Y cells.
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