817638-68-9Relevant articles and documents
Bichromophoric dyes for wavelength shifting of dye-protein fluoromodules
Pham, Ha H.,Szent-Gyorgyi, Christopher,Brotherton, Wendy L.,Schmidt, Brigitte F.,Zanotti, Kimberly J.,Waggoner, Alan S.,Armitage, Bruce A.
, p. 3699 - 3710 (2015)
Dye-protein fluoromodules consist of fluorogenic dyes and single chain antibody fragments that form brightly fluorescent noncovalent complexes. This report describes two new bichromophoric dyes that extend the range of wavelengths of excitation or emission of existing fluoromodules. In one case, a fluorogenic thiazole orange (TO) was attached to an energy acceptor dye, Cy5. Upon binding to a protein that recognizes TO, red emission due to efficient energy transfer from TO to Cy5 replaces the green emission observed for monochromophoric TO bound to the same protein. Separately, TO was attached to a coumarin that serves as an energy donor. The same green emission is observed for coumarin-TO and TO bound to a protein, but efficient energy transfer allows violet excitation of coumarin-TO, versus longer wavelength, blue excitation of monochromophoric TO. Both bichromophores exhibit low nanomolar KD values for their respective proteins, >95% energy transfer efficiency and high fluorescence quantum yields.
Clickable degradable aliphatic polyesters via copolymerization with alkyne epoxy esters: Synthesis and postfunctionalization with organic dyes
Teske, Nele S.,Voigt, Julia,Shastri, V. Prasad
, p. 10527 - 10533 (2014)
Degradable aliphatic polyesters are the cornerstones of nanoparticle (NP)-based therapeutics. In this paradigm, covalent modification of the NP with cell-targeting motifs and dyes can aid in guiding the NP to its destination and gaining visual confirmation. Therefore, strategies to impart chemistries along the polymer backbone that are amenable to easy modification, such as 1,3-dipolar cycloaddition of an azide to an alkyne (the click reaction ), could be significant. Here we present a simple and efficient way to introduce alkyne groups at high density in aliphatic polyesters without compromising their crystallinity via the copolymerization of cyclic lactones with propargyl 3-methylpentenoate oxide (PMPO). Copolymers of lactic acid and ε-caprolactone with PMPO were synthesized with up to 9 mol % alkyne content, and accessibility of the alkyne groups to the click reaction was demonstrated using several dyes commonly employed in fluorescence microscopy and imaging (Cy3, ATTO-740, and coumarin 343). In order to establish the suitability of these copolymers as nanocarriers, copolymers were formulated into NPs, and cytocompatibility, cellular uptake, and visualization studies undertaken in HeLa cells. Dye-modified NPs exhibited no quenching, remained stable in solution for at least 10 days, showed no cytotoxicity, and were readily taken up by HeLa cells. Furthermore, in addition to enabling the incorporation of multiple fluorophores within the same NP through blending of individual dye-modified copolymers, dye-modified polyesters offer advantages over physical entrapment of dye, including improved signal to noise ratio and localization of the fluorescence signal within cells, and possess the necessary prerequisites for drug delivery and imaging.
A Biocompatible Heterogeneous MOF–Cu Catalyst for In Vivo Drug Synthesis in Targeted Subcellular Organelles
Wang, Faming,Zhang, Yan,Liu, Zhengwei,Du, Zhi,Zhang, Lu,Ren, Jinsong,Qu, Xiaogang
supporting information, p. 6987 - 6992 (2019/04/14)
As a typical bioorthogonal reaction, the copper-catalyzed azide–alkyne cycloaddition (CuAAC) has been used for drug design and synthesis. However, for localized drug synthesis, it is important to be able to determine where the CuAAC reaction occurs in living cells. In this study, we constructed a heterogeneous copper catalyst on a metal–organic framework that could preferentially accumulate in the mitochondria of living cells. Our system enabled the localized synthesis of drugs through a site-specific CuAAC reaction in mitochondria with good biocompatibility. Importantly, the subcellular catalytic process for localized drug synthesis avoided the problems of the delivery and distribution of toxic molecules. In vivo tumor therapy experiments indicated that the localized synthesis of resveratrol-derived drugs led to greater antitumor efficacy and minimized side effects usually associated with drug delivery and distribution.
Development of an ‘OFF-ON-OFF’ fluorescent pH sensor suitable for the study of intracellular pH
Hirano, Tomoya,Noji, Yuki,Shiraishi, Takuya,Ishigami-Yuasa, Mari,Kagechika, Hiroyuki
, p. 4925 - 4930 (2016/07/19)
Changes of pH in living organisms are closely related to various physiological functions, so fluorescent sensors of pH would be useful as experimental tools and possibly also for medical diagnosis. We previously reported a pH sensor with ‘OFF-ON-OFF’ -type fluorescence change, which would be potentially more useful than conventional sensors with ‘OFF-ON’ type change. It can be utilized as a sensor for a specific range of pH, however, the range with strong fluorescence is relatively wide, around pH 7–10, which renders it impractical for use in biological studies. So in the present work, we adjusted the pH detection range by the introduction of chloro groups at the ortho-positions to the phenolic hydroxyl groups, whose deprotonation could control fluorescence change, and obtained a sensor specifically responsive to pH around 6. This sensor was confirmed to be suitable for fluorescence imaging of changes of intracellular pH in living cells.
