title: Impact of hydrophobic chain composition on amphiphilic macromolecule antiatherogenic bioactivity.
abstract: 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.
authors: Department of Chemistry and Chemical Biology, ‡Department of Biomedical Engineering, and §Department of Chemical and Biochemical Engineering, Rutgers University , Piscataway, New Jersey 08854, United States.
authors: Allison
authors: A
authors: Faig
authors: Latrisha K
authors: LK
authors: Petersen
authors: Prabhas V
authors: PV
authors: Moghe
authors: Kathryn E
authors: KE
authors: Uhrich
mesh_terms: D050197:Atherosclerosis; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051116:Receptors, Scavenger / Q000737:chemistry / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D051116:Receptors, Scavenger; C099252:oxidized low density lipoprotein; D011092:Polyethylene Glycols