Zhang, Shunyao; Tamura, Atsushi; Yui, Nobuhiko published their research in Science and Technology of Advanced Materials in 2021. The article was titled 《Weakly acidic carboxy group-grafted β-cyclodextrin-threaded acid-degradable polyrotaxanes for modulating protein interaction and cellular internalization》.Formula: C9H19NO4 The article contains the following contents:
To improve the therapeutic potential of β-cyclodextrin (β-CD)-threaded acid-degradable polyrotaxanes (β-CD PRXs) in cholesterol-related metabolic disorders, we investigated the effect of carboxylation of β-CD PRXs on intracellular uptake. In this study, we established a synthetic method for the modification of carboxylalkyl carbamates on β-CD PRXs without degradation and synthesized three series of carboxyalkyl carbamate group-modified β-CD PRXs with different alkyl spacer lengths. The modification of carboxymethyl carbamate (CMC), carboxyethyl carbamate (CEC), and carboxypropyl carbamate (CPC) on the β-CD PRXs slightly reduced the interaction of the PRXs with the lipid layer model compared with the modification of 2-(2-hydroxyethoxy)ethyl carbamate (HEE-PRX), which was used in our previous studies. However, all the carboxylated β-CD PRXs showed a significantly stronger interaction with a protein model compared with HEE-PRX. The carboxylated β-CD PRXs showed significantly high intracellular uptake, through macrophage scavenger receptor A (MSR-A)-mediated endocytosis, in MSR-A-pos. RAW 264.7 cells compared with HEE-PRX. Interestingly, the carboxylated β-CD PRXs also showed significantly higher intracellular uptake even in MSR-A-neg. cells compared with HEE-PRX. Carboxylated β-CD PRXs are considered to strongly interact with other membrane proteins, resulting in high intracellular uptake. The length of the alkyl spacer affected the intracellular uptake levels of carboxylated PRXs, however, this relationship was varied for different cell types. Furthermore, none of the carboxylated β-CD PRXs exhibited cytotoxicity in the RAW 264.7 and NIH/3T3 cells. Altogether, carboxylation of β-CD PRXs is a promising chem. modification approach for their therapeutic application because carboxylated β-CD PRXs exhibit high cellular internalization efficiency in MSR-A-neg. cells and negligible toxicity. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate(cas: 139115-91-6Formula: C9H19NO4)
tert-Butyl (2-(2-hydroxyethoxy)ethyl)carbamate(cas: 139115-91-6) belongs to ethers.Although ethers resist hydrolysis, they are cleaved by hydrobromic acid and hydroiodic acid. Hydrogen chloride cleaves ethers only slowly. Formula: C9H19NO4
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem