title: Amyloidogenic Properties of Short α-L-Glutamic Acid Oligomers.
abstract: Poly-L-glutamic acid (PLGA) forms amyloid-like β2-fibrils with the main spectral component of vibrational amide I' band unusually shifted below 1600 cm(-1). This distinct infrared feature has been attributed to the presence of bifurcated hydrogen bonds coupling C═O and N-D (N-H) groups of the main chains to glutamate side chains. Here, we investigate how decreasing the chain length of PLGA affects its capacity to form β2-fibrils. A series of acidified aqueous solutions of synthetic (l-Glu)n peptides (n ≈ 200, 10, 6, 5, 4, and 3) were incubated at high temperature. We observed that n = 4 is the critical chain length for which formation of aggregates with the β2-like infrared features is still observed under such conditions. Interestingly, according to atomic force microscopy (AFM), the self-assembly of (L-Glu)n chains varying vastly in length produces fibrils with rather uniform diameters of approximately 4-6 nm. Kinetic experiments on (L-Glu)5 and (L-Glu)200 peptides indicate that the fibrillation is significantly accelerated not only in the presence of homologous seeds but also upon cross-seeding, suggesting thereby a common self-assembly theme for (L-Glu)n chains of various lengths. Our results are discussed in the context of mechanisms of amyloidogenic fibrillation of homopolypeptides.
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , 00-927 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Hernik
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , 00-927 Warsaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Puławski
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , 00-927 Warsaw, Poland.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Fedorczyk
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , 00-927 Warsaw, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Tymecka
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , 00-927 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Misicka
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , 00-927 Warsaw, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Filipek
authors.affiliation: Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw , 00-927 Warsaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Dzwolak
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D007700:Kinetics; D018625:Microscopy, Atomic Force; D011099:Polyglutamic Acid / Q000737:chemistry*
chemical_list: D000682:Amyloid; D011099:Polyglutamic Acid