Interaction of intravenous immunoglobulin and three 20(S)-camptothecin analogs: maintaining higher circulatory levels of the biologically active species

Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin

“…The obtained K q (10 12 M −1 ·s −1 ) is larger than the maximum value of dynamic quenching rate constant of bimolecular diffusion collision, K q(max) (2.0 × 10 10 M −1 ·s −1 ), indicating that there exists a static quenching mechanism between the fluorophores and each CPT analogue arisen from the formation of a dark complex between the fluorophores and quenching agent. So, the dynamic quenching constant K SV can be interpreted as the association or binding constant of the reaction of complexation in this case [ 43 ]. On the other hand, most of the binding sites of IgG for antigen/semiantigen are located in the complement-determining region (CDR) of F(ab) 2 ( n = 2), however, the crystallizable fragment (complement-bing site, Fc) regions also considered to a certain extent to have similarity to F(ab) and can bind to smaller molecules [ 49 , 50 , 51 ], though there are more potential binding sites for IgG binding to antigen/semiantigen [ 52 , 53 , 54 ].…”

“…Based on the distinguishable UV-vis spectra of SN-38, 10-hydroxycamptothecin and topotecan between testing at pH 4.0, 7.4 and 10.0 in PBS (data shown in Table 4 ), the calculated ratios of lactone to total drug decrease from 90.40%, 86.68% and 34.47% in the absence of IVIG, to 86.47~87.35%, 56.56~68.58% and 29.76~32.71% in the presence of IVIG within the subsequent incubated 60 min at pH 7.40, respectively [ 43 ]. However, compared to the interaction of HSA with some CPTs at pH 7.4 either in PBS alone, HSA in PBS, plasma and human whole blood system, IVIG can maintain higher circulatory levels of lactone moieties of these CPTs [ 5 , 6 , 7 ], which indicates that IVIG preferentially binds the lactone form of the three CPTs and thereby preserves higher circulatory levels of the biologically active species at physiological pH 7.40.…”

“…As shown in the molecular docking plots ( Figure 4 ), the 7-ethyl-camptothecin molecule locates in the antigen-binding cleft composed of V L 26–32, V H 31–37, V L 90–95 and V H 96–99. As for the other analogues, the drug molecules mainly locate in the cleft composed of V L 26–32, V H 31–37, V L 48–55, V H 51–68, V H 84–91, V L 90–95, V H 96–99 and V H 101–110 [ 43 , 44 , 45 ]. Moreover, there is a hydrogen bond between an amino H provided from residue Arg 96 with atom N -1 of 7-ethylcamptothecin.…”

“…Molecular docking was carried out referring to the literature [ 43 ]. The drug structure was constructed with the Maestro [ 64 ] building tools.…”

“…Previously, the interaction of IVIG and several (20) S -configuration CPTs have been studied in vitro [ 43 , 44 , 45 ] and study reveals that IVIG can maintain higher circulatory levels of lactone moieties of three CPTs at physiological pH 7.40 compared to HSA [ 45 ]. In this study, as one of camptothecin analogues, the binding performance of 7-ethylcamptothecin and IVIG will be investigated in vitro, further the binding properties of IVIG and six (20) S -configuration of CPTs with different substituents at A -ring and/or B -ring will be collected together and compared each other.…”