Chemistry Reference
In-Depth Information
Aparatus constant by cell culture time
0.12
0.1
0.08
0.06
0.04
0.02
0
0
10
20
30
40
50
60
-0.02
Culture time (hr)
Fig. 6.46
Relationship between the inhibition rate constant
C
1 and paclitaxel concentration
The results also provide evidence that the DMC/PTX complex causes a supramo-
lecular reaction involving allosteric promotion, as in Eq. (
6.46
) The Hill coefficient
included in Eq. (
6.46
) supports the likelihood of allosteric cooperation as it
represents the strength of cooperative molecular joints. These phenomena may
depend on the supramolecular characteristics of clathrate compounds as the pacli-
taxel guest is complexed with DDMC as the host.
This is certified by the strong photoconductive property of DDMC/PTX com-
plex, promoting
π
-electron resonance as shown in Fig.
6.42
. Therefore, the DDMC/
PTX complex shows marked substrate specificity, consistent with artificial
enzymes. This substrate specificity of the DDMC/PTX complex promotes a reac-
tion between paclitaxel and tubulin, the target of paclitaxel, and avoids potential
interference from changes in gene expression that may affect the survival response
to paclitaxel, even at low concentrations.
Paclitaxel can be conjugated to a variety of carriers, including polyglutamate and
albumin, or encapsulated in cationic liposomes. Using these carriers, paclitaxel is
thought to be transported into and released directly in cells, thus improving its
efficacy. However, the DDMC/PTX complex is not degraded in the cell, and its
efficacy may be enhanced by remaining in supramolecular form.
6.5.8 Thermodynamic Consideration of Supramolecular
Allosteric Binding
Promotion of supramolecular allosteric binding of the ligand (as when molecular
oxygen binds to hemoglobin) is a phenomenon that increases the reactivity of the
active site and other substrate molecule binding sites.
In the case of hemoglobin, the oxygen works efficiently as an effector, and at the
same time as the substrate. Allosteric binding to one subunit affects the binding of
substrate to the next subunit, enhancing the affinity of binding sites remaining by its
