title: Self-aggregation of a polyalanine octamer promoted by its C-terminal tyrosine and probed by a strongly enhanced vibrational circular dichroism signal.
abstract: The eight-residue alanine oligopeptide Ac-A(4)KA(2)Y-NH(2) (AKY8) was found to form amyloid-like fibrils upon incubation at room temperature in acidified aqueous solution at peptide concentrations >10 mM. The fibril solution exhibits an enhanced vibrational circular dichroism (VCD) couplet in the amide I' band region that is nearly 2 orders of magnitude larger than typical polypeptide/protein signals in this region. The UV-CD spectrum of the fibril solution shows CD in the region associated with the tyrosine side chain absorption. A similar peptide, Ac-A(4)KA(2)-NH(2) (AK7), which lacks a terminal tyrosine residue, does not aggregate. These results suggest a pivotal role for the C-terminal tyrosine residue in stabilizing the aggregation state of this peptide. It is speculated that interactions between the lysine and tyrosine side chains of consecutive strands in an antiparallel arrangement (e.g., cation-pi interactions) are responsible for the stabilization of the resulting fibrils. These results offer considerations and insight regarding the de novo design of self-assembling oligopeptides for biomedical and biotechnological applications and highlight the usefulness of VCD as a tool for probing amyloid fibril formation.
authors: Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, Pennsylvania 19104, USA.
authors: Thomas J
authors: TJ
authors: Measey
authors: Kathryn B
authors: KB
authors: Smith
authors: Sean M
authors: SM
authors: Decatur
authors: Liming
authors: L
authors: Zhao
authors: Guoliang
authors: G
authors: Yang
authors: Reinhard
authors: R
authors: Schweitzer-Stenner
mesh_terms: D000682:Amyloid; D002942:Circular Dichroism / Q000379:methods*; D019281:Dimerization; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D000682:Amyloid; D009842:Oligopeptides; D010455:Peptides; C019529:polyalanine; D014443:Tyrosine