title: Inhibition of amyloid peptide fragment Aβ25-35 fibrillogenesis and toxicity by N-terminal β-amino acid-containing esapeptides: is taurine moiety essential for in vivo effects?
abstract: We report the synthesis and fibrillogenesis inhibiting activity of the new peptide derivatives 1-4, related to the pentapeptide Ac-LPFFD-NH(2)  (iAβ5p), proposed by Soto and co-workers and widely recognized as one of the most active β-sheet breaker agents. The Aβ(25-35)  fragment of the parent full-length Aβ(1-42)  was used as fibrillogenesis model. The activity of peptide derivatives 1-4 was tested in vitro by thioflavin T binding assay, far UV CD spectroscopy, and scanning electron microscopy. Their ability to hinder the toxic effect of Aβ(25-35) in vivo was studied by monitoring the viability of human SH-SY5Y neuroblastoma cells and the prevention of superoxide anion radical release from BV2 microglial cells. The results point to a favourable role in the fibrillogenesis inhibitory activity of the sulphonamide junction for compounds 1 and 2, containing an N,N-dimethyltaurine and a taurine amino-terminal moiety, respectively. Furthermore, compounds 1 and 2 show a significant protective effect on cell viability, rescuing the cells from the toxicity exerted by Aβ(25-35)  treatment.
authors: Istituto di Chimica Biomolecolare del CNR, Sapienza Università di Roma, Piazzale A. Moro 5, Rome, Italy. cesare.giordano@uniroma1.it
authors: Cesare
authors: C
authors: Giordano
authors: Anna
authors: A
authors: Sansone
authors: Annalisa
authors: A
authors: Masi
authors: Alessandra
authors: A
authors: Masci
authors: Luciana
authors: L
authors: Mosca
authors: Roberta
authors: R
authors: Chiaraluce
authors: Alessandra
authors: A
authors: Pasquo
authors: Valerio
authors: V
authors: Consalvi
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D052160:Benzothiazoles; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D006801:Humans; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013481:Superoxides / Q000378:metabolism; D013654:Taurine / Q000737:chemistry*; D013844:Thiazoles / Q000378:metabolism
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D010446:Peptide Fragments; D010455:Peptides; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); D013481:Superoxides; D013654:Taurine; C009462:thioflavin T