Synthesis and activity of fibrillogenesis peptide inhibitors related to the 17–21 β-amyloid sequence

Peptide derivatives 1– 5, incorporating synthetic non-proteinogenic amino acids, related to the β-amyloid 17–21 fragment of the amyloidogenic Aβ 1–40, and the N-protected decapeptide 6, corresponding to a dimeric sequence of the same fragment, have been synthesized. These compounds were designed by...

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Veröffentlicht in:European journal of medicinal chemistry 2009, Vol.44 (1), p.179-189
Hauptverfasser: Giordano, Cesare, Masi, Annalisa, Pizzini, Aldo, Sansone, Anna, Consalvi, Valerio, Chiaraluce, Roberta, Lucente, Gino
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container_end_page 189
container_issue 1
container_start_page 179
container_title European journal of medicinal chemistry
container_volume 44
creator Giordano, Cesare
Masi, Annalisa
Pizzini, Aldo
Sansone, Anna
Consalvi, Valerio
Chiaraluce, Roberta
Lucente, Gino
description Peptide derivatives 1– 5, incorporating synthetic non-proteinogenic amino acids, related to the β-amyloid 17–21 fragment of the amyloidogenic Aβ 1–40, and the N-protected decapeptide 6, corresponding to a dimeric sequence of the same fragment, have been synthesized. These compounds were designed by using Soto's pentapeptide Ac–LPFFD–NH 2 (iAβ5p) as lead compound. Their activity as inhibitors of fibrillogenesis and stability against enzymatic degradation have been determined. Compounds 1, 5 and 6 are potent inhibitors in comparison to the lead compound. Exposure to chymotrypsin of peptide derivatives 1– 5, all containing unnatural amino acids, shows increased stability as compared with iAβ5p and 6. Conformational properties of the new compounds have been determined by CD and FT-IR spectroscopies. [Display omitted] Synthesis, properties and activity of novel analogues ( 1– 6) of the known Ac–Leu-Pro-Phe-Phe-Asp(OH)–NH 2 (iAβ5p) fibrillogenesis pentapeptide inhibitor are reported.
doi_str_mv 10.1016/j.ejmech.2008.03.036
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subjects Aggregation inhibitor
Alzheimer's disease
Amino Acid Sequence
Amyloid - antagonists & inhibitors
Amyloid beta-Peptides - antagonists & inhibitors
Biological and medical sciences
Drug Design
Drug Stability
Fibrillogenesis
Fluorescence assay
Humans
Medical sciences
Molecular Conformation
Neuropharmacology
Peptide Fragments - antagonists & inhibitors
Peptide Fragments - chemical synthesis
Pharmacology. Drug treatments
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Scanning electron microscopy
Structure-Activity Relationship
β-Amyloid
title Synthesis and activity of fibrillogenesis peptide inhibitors related to the 17–21 β-amyloid sequence
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