Impact of Hydrophobic Chain Composition on Amphiphilic Macromolecule Antiatherogenic Bioactivity

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• 作者：Allison Faig ; Latrisha K. Petersen ; Prabhas V. Moghe ; Kathryn E. Uhrich
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：September 8, 2014
• 年：2014
• 卷：15
• 期：9
• 页码：3328-3337
• 全文大小：502K
• ISSN：1526-4602

文摘

Amphiphilic macromolecules (AMs) composed of sugar backbones modified with branched aliphatic chains and a poly(ethylene glycol) (PEG) tail can inhibit macrophage uptake of oxidized low-density lipoproteins (oxLDL), a major event underlying atherosclerosis development. Previous studies indicate that AM hydrophobic domains influence this bioactivity through interacting with macrophage scavenger receptors, which can contain basic and/or hydrophobic residues within their binding pockets. In this study, we compare two classes of AMs to investigate their ability to promote athero-protective potency via hydrogen-bonding or hydrophobic interactions with scavenger receptors. A series of ether-AMs, containing methoxy-terminated aliphatic arms capable of hydrogen-bonding, was synthesized. Compared to analogous AMs containing no ether moieties (alkyl-AMs), ether-AMs showed improved cytotoxicity profiles. Increasing AM hydrophobicity via incorporation of longer and/or alkyl-terminated hydrophobic chains yielded macromolecules with enhanced oxLDL uptake inhibition. These findings indicate that hydrophobic interactions and the length of AM aliphatic arms more significantly influence AM bioactivity than hydrogen-bonding.