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. 2020 Sep 21;59(41):4003–4014. doi: 10.1021/acs.biochem.0c00443

Table 1. Summary of the Apparent Rate Constants for Tau Aggregation in the Presence of Unmodified Heparin and Desulfated Derivatives, Obtained from the Lines of Best Fit to the Data in Figure 2a.

cofactor conc/μM kn/10–6 M–1 s–1 k+/106 M–1 s–1 k2/M–2 s–1 t0.5/h
LMWH 2.5 32 17 10 0.51 (0.10)
5.0 35 19 10 0.46 (0.10)
10.0 33 18 70 0.45 (0.10)
20.0 6 4 1 1.70 (0.13)
LMW-6OH 2.5 4 7 13 1.47 (0.24)
5.0 6 9 12 1.12 (0.14)
10.0 9 15 16 0.72 (0.12)
20.0 6 11 16 0.95 (0.06)
LMW-NAc 2.5 6 4 10 1.4 (0.13)
5.0 5 6 10 1.4 (0.15)
10.0 5 8 11 0.9 (0.10)
20.0 3 4 10 1.7 (0.10)
LWM-2OH 2.5 1 2 1 6.5 (0.25)
5 2 2 1 5.5 (0.30)
10 2 3 1 4.4 (0.30)
20 2 2 0  
HWMH 2.5 36 19 10 0.5 (0.03)
5 28 15 9 0.5 (0.09)
10 6 4 6 2.0 (0.05)
HMW-6OH 2.5 11 7 1 1.7 (0.09)
5 10 7 1 1.6 (0.1)
HMW-2OH 2.5       >6
2.5        
a

The calculations were also based on fixed values for the fibril dissociation rate constant (km = 1.0 M–1 s–1) and the reaction orders of primary nucleation (nc = 2) and secondary nucleation (n2 = 2).27,28 The reaction orders do not necessarily correspond to the size of the nuclei, but heparin has been shown to interact with two tau molecules, forming a dimer that nucleates fibril growth.31 Dashes indicate where constants could not be calculated because of poor fits to the experimental data. Errors in t0.5 are given in parentheses.