Reversal of Aggregation Using β-Breaker Dipeptide Containing Peptides: Application to Aβ_(1–40) Self-Assembly and Its Inhibition

Abstract

Reversion of protein or peptide aggregation is a formidable task, important in various domains of research at the interface of chemistry, medicine, and nanoscience. A novel class of dipeptides, termed as β-breaker dipeptides (BBDPs), is identified, which can be incorporated into the self-recognizing sequences to generate a novel class of conformational switch which forms β-sheet at an initial stage and then converts in a controlled manner to random coil at specific conditions. Incorporation of BBDPs in a well designed amyloidogenic peptides generates a special class of β-sheet breaker peptides those undergo a chemical change at physiological condition generating a breaker element in situ. These β-breaker peptides are shown to first incorporate into the amyloid and then disrupt it. Such conformational switches may be used to study agrregation/disaggregation process and may find many biomedical applications relevant to aggregation related disorders. Such strategy for reversion of peptide aggregation using chemical tricks may find application in material chemistry as well.

Disaggregation of Amylin Aggregate by Novel Conformationally Restricted Aminobenzoic Acid containing α/β and α/γ Hybrid Peptidomimetics

“…To perform the CD study, 400 μL of the sample was taken in a cuvette and measured ellipticity with bandwidth of 1 mm20. Three measurements were accumulated.…”

“…Thus, targeting the small peptide fragments and designing small peptide based inhibitor comprised of breaker element and recognition segment is accepted as a promising therapeutic approach against amyloid formation and its disruption. Many small peptide based inhibitors with various breaker elements are reported in literature, including proline16, α-aminoisobutyric acid (Aib)17, α,β-dehydrophenylalanine18, N -methylated amino acids19 and aspartic acid derivative20. Among them, the first three types of breaker peptides are designed by the insertion of conformational restriction in it.…”

Biophysical insight into the anti-amyloidogenic behavior of taurine

“…Small molecules such as polyphenols, metal ions, vitamins, nucleotides and synthetic peptides have been reported as anti-aggregation agents [12][13][14].…”

Feasibility of β-Sheet Breaker Peptide-H102 Treatment for Alzheimer's Disease Based on β-Amyloid Hypothesis

“…While, the synthetic of beta-sheet structure can be a potential therapeutic strategy for AD, as it is capable of binding A-beta but unable to become part of a beta-sheet structure, thus inhibiting the peptide aggregation [30]. β-sheet breaker peptides are specifically synthesized inhibitors against Aβ aggregation, which have been developed as drugs for the treatment of AD.…”