Table 2. Affinity Constants (K_a) of the Compounds for Binding to MTs and Effect of Single-Point Ligand Changes on the Binding Affinity of the Ligands for MTs.

Ka (107 M–1)
ligand	26 °C	27 °C	30 °C	32 °C	35 °C	37 °C	40 °C	42 °C	ΔG 35 °C (kJ mol–1)
paclitaxel3	2.64 ± 0.2	2.19 ± 0.05	1.83 ± 0.1	1.81 ± 0.2	1.43 ± 0.2	1.07 ± 0.1	0.96 ± 0.1	0.94 ± 0.2	–42.2 ± 0.4
docetaxel3	6.95 ± 0.4	6.57 ± 0.5	5.42 ± 0.4	4.89 ± 0.4	3.93 ± 0.3	3.09 ± 0.2	2.89 ± 0.2	2.38 ± 0.1	–44.8 ± 0.2
dictyostatin3	35.5 ± 7	32.0 ± 5.5	24.8 ± 3	23.1 ± 3	19.2 ± 2.5	16.8 ± 2	14.1 ± 2	14.2 ± 2	–48.8 ± 0.4
2	0.0051 ± 0.003	0.0050 ± 0.003	0.0047 ± 0.003	0.0048 ± 0.0035	0.0041 ± 0.0026	0.0035 ± 0.002	0.0037 ± 0.001	0.0035 ± 0.002	–27.2 ± 1.2
discodermolide3	872 ± 82	837 ± 77	958 ± 134	704 ± 95	555 ± 111	526 ± 72	547 ± 60	321 ± 73	–57.4 ± 0.5
5	2.4 ± 1.2	2.5 ± 1.1	2.6 ± 1.2	2.4 ± 1.2	2.2 ± 0.4	2.2 ± 0.45	1.9 ± 0.25	1.87 ± 0.4	–43.3 ± 0.4
7	0.06 ± 0.02	0.05 ± 0.02	0.06 ± 0.01	0.07 ± 0.01	0.06 ± 0.01	0.06 ± 0.02	0.04 ± 0.01	0.04 ± 0.2	–34.4 ± 0.4
8	2.1 ± 0.4	1.9 ± 0.5	1.7 ± 0.3	1.7 ± 0.4	1.6 ± 0.2	1.4 ± 0.2	1.4 ± 0.2	1.2 ± 0.3	–42.5 ± 0.3
10	0.62 ± 0.3	0.66 ± 0.3	0.57 ± 0.2	0.62 ± 0.25	0.54 ± 0.2	0.51 ± 0.2	0.49 ± 0.2	0.45 ± 0.2	–39.7 ± 0.8
11	0.33 ± 0.05	0.36 ± 0.1	0.29 ± 0.09	0.27 ± 0.07	0.28 ± 0.05	0.25 ± 0.01	0.3 ± 0.02	0.23 ± 0.02	–38.0 ± 0.4
13	1.13 ± 0.3	1.12 ± 0.3	0.98 ± 0.2	0.95 ± 0.15	0.73 ± 0.1	0.71 ± 0.1	0.56 ± 0.1	0.58 ± 0.08	–40.4 ± 0.3
14	0.07 ± 0.03	0.055 ± 0.02	0.043 ± 0.01	0.04 ± 0.006	0.033 ± 0.005	0.025 ± 0.004	0.029 ± 0.004	0.028 ± 0.01	–32.5 ± 0.4
15	0.29 ± 0.1	0.29 ± 0.1	0.3 ± 0.1	0.33 ± 0.07	0.32 ± 0.1	0.33 ± 0.2	0.4 ± 0.2	0.28 ± 0.05	–38.3 ± 0.7
16	0.32 ± 0.2	0.4 ± 0.2	0.4 ± 0.1	0.4 ± 0.1	0.35 ± 0.08	0.35 ± 0.1	0.3 ± 0.1	0.25 ± 0.07	–38.6 ± 0.5

	Ka (107 M–1)
ligand	25 °C	30 °C	35 °C	40 °C	ΔG 35 °C (kJ mol–1)
4	119.3 ± 3	68.5 ± 8	53.8 ± 4.8	34 ± 1.3	51.5 ± 0.2
6	88.1 ± 14	55 ± 3	32.6 ± 3.4	26.4 ± 2.5	50.2 ± 0.3
9	229.7 ± 22	175 ± 16.5	113.8 ± 3.25	63.4 ± 2	53.4 ± 0.1
12	106.4 ± 32	75.1 ± 4	65.2 ± 2.6	32.2 ± 1.5	51.9 ± 0.1

change	description	ΔΔG 35 °C (kJ mol–1)
1 → 4	removal of C6 methyl	–2.7
1 → 5	reduction of C10=C11 double bond	+5.5
12 → 13		+11.5
1 → 6	reduction of C2=C3 double bond	–1.4
1 → 10	removal of C16 methyl	+9.1
11 → 7		+3.6
1 → 11	epimerization of C9 hydroxyl	+10.8
10 → 7		+5.3
15 → 16		–0.3
6 → 8	reduction of C4=C5 double bond	+6.1
1 → 9	methylation of C9 hydroxyl	–4.6
12 → 15	reduction of C4=C5 double bond and hydroxylation at C5	+13.6
12 → 14	introduction of docetaxel side chain at C7	+19.4
1 → 14	esterification of C7 hydroxyl	+9.7