Tryptophan–glucosamine conjugates modulate tau-derived PHF6 aggregation at low concentrations

Abstract

Tryptophan–glucosamine conjugates efficiently inhibit tau-derived PHF6-peptide fibrillization and disrupt its preformed fibrils at very low concentrations.

Rational Design of a Cocktail of Inhibitors against Aβ Aggregation

“…To begin with, we first evaluated the effects of Trp‐glucose conjugates on Aβ aggregation . It was reported that tryptophan derived molecules could inhibit the aggregation of some amyloid proteins, including Aβ .…”

“…Thus, we looked forward to achieving a better inhibitory effect by covalently linking Trp and glucose. As previously described, we successfully got the Trp‐glucose conjugates ASn ( n =1,2,3. Scheme ).…”

“…Thus, we looked forward to achieving ab etter inhibitory effect by covalently linking Trpa nd glucose. As previously described, [7] we successfully gott he Trp-glucose conjugates ASn (n = 1,2,3. Scheme 1).We then conducted ThTk inetics assay to test whether these conjugates could inhibit the aggregation of Ab.…”

“…As av alidation of our idea, here we showed that am ixture of Trp-glucose conjugates and some natural products could indeed achieve the co-inhibition of Ab aggregation.To begin with, we first evaluated the effects of Trp-glucose conjugates on Ab aggregation. [7] It was reported that tryptophan derived molecules could inhibitt he aggregation of some amyloid proteins, [8] including Ab. [9] Meanwhile, polyhydroxy compounds, including inositols [10] and polyphenols, [11] have been shown to be ablet or educe the amount (or toxicity) of Ab oligomers.…”

Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity

“…The conjugation of glycans to peptides increases the overall interaction surface of the hybrid molecules, therefore increasing solubility by expanding the number of possible interactions with the solvent 50 – 53 . Along the same rationale, aromatic molecules, which display high potential as anti-amyloidogenic agents, but are by themselves hydrophobic, were conjugated to mannitol and glucosamine 43 , 54 .…”