Self‐assembly of β‐turn motif‐connected tandem repeats of Aβ_16‐22 and its aromatic analogs

Abstract

Self‐assembly of peptides and proteins into aggregates with a signature of cross‐β conformation is a hallmark of amyloids. Short peptides have provided important insights in understanding the various interactions that drive self‐assembly as well as the molecular architecture of the self‐assembled structures. The short amyloidogenic‐stretch of β‐amyloid, Aβ16‐22 (Ac‐KLVFFAE‐am), is a good model peptide to study the aspects of β‐amyloid fibril formation. In order to investigate how a turn‐supporting sequence could modulate the interaction of the Ac‐KLVXZAE‐am chains, where X and Z are the aromatic amino acids, Phe, Tyr, or Trp, we investigated the self‐assembly of Ac‐KLVFFAE‐am, Ac‐KLVFYAE‐am, Ac‐KLVYYAE‐am, and Ac‐KLVWWAE‐am separated by turn‐inducing dipeptide motifs, Asn‐Gly, DPro‐Gly, and Aib‐DPro. The peptides harboring β‐turn‐inducing motifs aggregate rapidly causing large enhancements in thioflavin T (ThT) fluorescence compared to control, β‐turn motif lacking peptides. The morphology of fibrils strongly depends on the type of β‐turn. Ac‐KLVFYAE‐am repeats separated by Aib‐DPro and DPro‐Gly have the highest aggregation propensity among all the peptides studied; they caused very large enhancement in ThT fluorescence. Ac‐KLVYYAE‐am is largely non‐amyloidogenic; the DPro‐Gly and Aib‐DPro connected repeats, however, resulted in distinct fibrils that bind ThT. The study indicates that β‐turn motifs can be exploited to modulate and control the aggregation propensity of peptides and the morphology of aggregates.

Hydrogel Formation by an Aromatic Analogue of a β-Amyloid Fragment, Aβ16–22: A Scaffold for 3D Cell Culture

“…The peptides were dissolved in dimethyl sulfoxide and purified on a reversedphase C18 column, as described previously. 43 The purified peptides were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF).…”

“…The data were converted to mean residue ellipticity, as previously described. 43 Fourier Transform Infrared (FTIR) Spectroscopy. FTIR spectra were recorded for the 24 h old 2 mM peptide samples on a Shimadzu IRAffinity-1S Fourier transform infrared spectrophotometer on the attenuated total reflection (ATR) module equipped with a diamond ATR crystal.…”

“…The peptides were precipitated in ice-cold diethyl ether, washed with diethyl ether to remove the scavengers, and dried. The peptides were dissolved in dimethyl sulfoxide and purified on a reversed-phase C18 column, as described previously . The purified peptides were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF).…”

The β‐turn‐supporting motif in the polyglutamine binding peptide QBP1 is essential for inhibiting huntingtin aggregation

“…Each spectrum is the average of 8 scans. The data were converted to mean residue ellipticity ([θ] MRE ) as described elsewhere [16].…”

Ultrashort Peptide Self-Assembly: Front-Runners to Transport Drug and Gene Cargos

“…The modes of interaction in general are π-π stackings, hydrophobic associations, electrostatic interactions, and hydrogen-bonding. Various morphologies based on free and protected H-Phe-Phe-OH molecule (Ribeiro et al, 2019) and its analogs/derivatives forming fibrils (Reches and Gazit, 2005), vesicles (Guo et al, 2012), tubes (Reches and Gazit, 2006), wires (Huang et al, 2014;Marchesan et al, 2015b), plates (Tamamis et al, 2009), sheets, flakes , necklaces (Yuran et al, 2012) could be demonstrated by manipulating the stimuli and physical/chemical conditions (Adler-Abramovich and Datta et al, 2018Datta et al, , 2019. Concentration dependent ordered nanoarchitectures such as planar bilayers and other diverse shapes of vesicles, namely, discoid, toroid, ellipsoid, and pot-shaped, have been reported by Guo et al (2012).…”