Thermodynamics of the association of transthyretin and its nanovectorized form with heparan sulfate proteoglycan HPLC stationary phase and correlation with tetramer stability and amyloidogenicity

As transthyretin (TTR) can prevent A? aggregation, a key protein in Alzheimer disease (AD), we developed a novel nanovector based on single wall carbon nanotubes (SWCNTs) functionalized by TTR. The retention factors (k) of the binding of grafted TTR on SWCNT (abbreviated gTTR) to HSPG were determined using an immobilized HSPG stationary phase. The negative values of the thermodynamic data demonstrated that van der Waals and hydrogen bonds played a major role in the binding at all pHs value. This binding was maximal at acidic conditions due to ionic interactions between the protonated His of gTTR with the negatively charged sulfate groups of HSPG. The weaker binding to HSPG for gTTR (k?=?3.70 at pH = 4.00 and 37??C) than free TTR (abbreviated fTTR) (k?=?11.80 at pH = 4.00 and 37??C) observed at acidic pHs was explained by the least facility of the His residue to be protonated when TTR was grafted on carbon nanotube. The nanovectorization of TTR with SWCNT thus stabilized the TTR tetramer structure and decreased the amyloid formation of TTR. Fibril formation of fTTR and gTTR studied by turbidity confirmed the fact that immobilization of TTR on SWCNTs decreased the extent and rate of amyloid fibril formation relative to free TTR.