Tartaric acid-based amphiphilic macromolecules with ether linkages exhibit enhanced repression of oxidized low density lipoprotein uptake

Abstract

Cardiovascular disease initiates with the atherogenic cascade of scavenger receptor- (SR-) mediated oxidized low-density lipoprotein (oxLDL) uptake. Resulting foam cell formation leads to lipid-rich lesions within arteries. We designed amphiphilic macromolecules (AMs) to inhibit these processes by competitively blocking oxLDL uptake via SRs, potentially arresting atherosclerotic development. In this study, we investigated the impact of replacing ester linkages with ether linkages in the AM hydrophobic domain. We hypothesized that ether linkages would impart flexibility for orientation to improve binding to SR binding pockets, enhancing anti-atherogenic activity. A series of tartaric acid-based AMs with varying hydrophobic chain lengths and conjugation chemistries were synthesized, characterized, and evaluated for bioactivity. 3-D conformations of AMs in aqueous conditions may have significant effects on anti-atherogenic potency and were simulated by molecular modeling. Notably, ether-linked AMs exhibited significantly higher levels of inhibition of oxLDL uptake than their corresponding ester analogues, indicating a dominant effect of linkage flexibility on pharmacological activity. The degradation stability was also enhanced for ether-linked AMs. These studies further suggested that alkyl chain length (i.e., relative hydrophobicity), conformation (i.e., orientation), and chemical stability play a critical role in modulating oxLDL uptake, and guide the design of innovative cardiovascular therapies.

Design of Video Surveillance System based on Power Line Carrier and RFID

“…Integrated nested vectors interrupt controlling. Its greatest advantage lies in integrating 100 MHz Ethernet when compared with other controllers [3]. When intelligent control center and master controller are in different LANs, computer connects with WAN through router.…”

Design and Implementation of e-mail Client Application

“…Through the connection of the world's Internet, to achieve all kinds of signal transmission, receiving, storage and other processing, mail to the world in every corner. So far, can be said that e-mail is the most used Internet resources as a service, E-mai1 not limited to letters of transfer, can also be used to transfer files, voice and graphics, images of different types of information [1]. E-mail is not a "end-to-end" service, which is called "storage and forwarding" service.…”

Fault Diagnosis of Transformer for Auxiliary Power Supply of Photovoltaic Micro Inverter

“…That is, based on the state of the equipment, maintenance mode is formed by forecasting the development trend of equipment status, so as to provide value-added services for special transformer users. At present, the threshold method is used to identify and locate the fault [4], but there are limitations and lags in this method. Due to the power supply equipment has various data types, large data and other characteristics, big data technology is introduced into equipment state detection to conduct abnormal state detection of equipment by big data analysis.…”