Design, synthesis, and biological evaluation of glycine-based molecular tongs as inhibitors of Abeta1-40 aggregation in vitro.
A series of N-terminus benzamides of glycine-based symmetric peptides, linked to m-xylylenediamine and 3,4'-oxydianiline spacers, were prepared and tested as inhibitors of beta-amyloid peptide Abeta(1-40) aggregation in vitro. Compounds with good anti-aggregating activity were detected. Polyphenolic amides showed the highest anti-aggregating activity, with IC(50) values in the micromolar range. Structure-activity relationships suggested that pi-pi stacking and hydrogen-bonding interactions play a key role in the inhibition of Abeta(1-40) self-assembly leading to amyloid fibrils.
Cellamare
Saverio
S
Dipartimento Farmaco-chimico, Università degli Studi di Bari, Via Orabona 4, 70125 Bari, Italy.
Stefanachi
Angela
A
Stolfa
Diana A
DA
Basile
Teodora
T
Catto
Marco
M
Campagna
Francesco
F
Sotelo
Eddy
E
Acquafredda
Pasquale
P
Carotti
Angelo
A
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000814:Aniline Compounds / Q000737:chemistry; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002109:Caffeic Acids; D015195:Drug Design; D005998:Glycine / Q000737:chemistry*; D015394:Molecular Structure; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010647:Phenyl Ethers / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D014992:Xylenes / Q000737:chemistry
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001549:Benzamides; D002109:Caffeic Acids; D010446:Peptide Fragments; D010455:Peptides; D010647:Phenyl Ethers; D014992:Xylenes; C078592:amyloid beta-protein (1-40); C066883:1,3-xylenediamine; C093786:phenylethyl 3-methylcaffeate; D005998:Glycine