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Impact of Hydrophobic Chain Composition on Amphiphilic Macromolecule Antiatherogenic Bioactivity
[Image: see text] 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 stu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157764/ https://www.ncbi.nlm.nih.gov/pubmed/25070717 http://dx.doi.org/10.1021/bm500809f |
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author | Faig, Allison Petersen, Latrisha K. Moghe, Prabhas V. Uhrich, Kathryn E. |
author_facet | Faig, Allison Petersen, Latrisha K. Moghe, Prabhas V. Uhrich, Kathryn E. |
author_sort | Faig, Allison |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-4157764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-41577642015-07-28 Impact of Hydrophobic Chain Composition on Amphiphilic Macromolecule Antiatherogenic Bioactivity Faig, Allison Petersen, Latrisha K. Moghe, Prabhas V. Uhrich, Kathryn E. Biomacromolecules [Image: see text] 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. American Chemical Society 2014-07-28 2014-09-08 /pmc/articles/PMC4157764/ /pubmed/25070717 http://dx.doi.org/10.1021/bm500809f Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) |
spellingShingle | Faig, Allison Petersen, Latrisha K. Moghe, Prabhas V. Uhrich, Kathryn E. Impact of Hydrophobic Chain Composition on Amphiphilic Macromolecule Antiatherogenic Bioactivity |
title | Impact of Hydrophobic
Chain Composition on Amphiphilic
Macromolecule Antiatherogenic Bioactivity |
title_full | Impact of Hydrophobic
Chain Composition on Amphiphilic
Macromolecule Antiatherogenic Bioactivity |
title_fullStr | Impact of Hydrophobic
Chain Composition on Amphiphilic
Macromolecule Antiatherogenic Bioactivity |
title_full_unstemmed | Impact of Hydrophobic
Chain Composition on Amphiphilic
Macromolecule Antiatherogenic Bioactivity |
title_short | Impact of Hydrophobic
Chain Composition on Amphiphilic
Macromolecule Antiatherogenic Bioactivity |
title_sort | impact of hydrophobic
chain composition on amphiphilic
macromolecule antiatherogenic bioactivity |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157764/ https://www.ncbi.nlm.nih.gov/pubmed/25070717 http://dx.doi.org/10.1021/bm500809f |
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