Reply to Comment on a??Photo-Controlled Reversible Microtubule Assembly Mediated by Paclitaxel-Modified Cyclodextrina??
DOI:10.1002/ange.202000894
期刊:Angewandte Chemie
出版年份:2020
更新时间:2025-09-23 15:19:57
摘要:
In a Correspondence on our previous study ?Photo-Controlled Reversible Microtubule Assembly Mediated by Paclitaxel-Modified Cyclodextrin“ published in this journal in 2018,[1a] Thorn-Seshold comments on our results.[1b] First of all, we would like to appreciate his comments and interest in our work. The aggregation behavior of microtubules (MTs) in our work has been demonstrated from the viewpoint of macrocycle-based host–guest complexation at the supramolecular level and subsequently, the MT stabilizers based on azobenzene-modified paclitaxel (PTX) derivatives as photoswitchable small molecules have been investigated by Thorn-Seshold and co-workers in 2019.[2] In our case, the microscopy results showed that the MT morphology was dramatically affected by the photoisomeric complexation between cyclodextrin (CD) and arylazopyrazole (AAP). No fibrous assembly as free MT could be observed in the presence of free PTX-CD, PTX-AAP, or their inclusion complex in the cis/trans states. Therefore, the introduction of CD and AAP definitely influenced the self-assembling behavior between PTX and MT. Moreover, fluorescent-dye-staining assays demonstrated that the PTX-derived host and guest compounds still possessed MT-targeting ability to some extent, because MT could be co-labeled by FITC-tagged antibodies and adamantane-containing RhB. Thus, the microtubular aggregation was proposed as one of the possible assembling modes in Scheme 1 (cartoon presentation). The binding mode of MT with CD and AAP was directly deduced from our microscopy images and cellular confocal experiments. The biological effect in our work may be jointly attributed to both the PTX-dependent pathway (PTX-induced microtubular stabilization) and the PTX-independent pathway (complexation-induced multivalent supramolecular cross-linkage) at the nanometer scale.[3] Under these circumstances, one reasonable explanation is that the latter (independent) effect may become comparable to the former (dependent) one when the MT affinity is reduced by chemical modification at the 2’-OH position of PTX.
作者:
Ying-Ming Zhang,Qilin Yu,Yu Liu