Journal article
Structure Activity Relations of Nanolipoblockers with the Atherogenic Domain of Human Macrophage Scavenger Receptor A
Biomacromolecules, v 10(6), pp 1381-1391
08 Jun 2009
PMID: 19405544
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Oxidized low density lipoprotein (oxLDL) uptake by macrophages is mediated by scavenger receptors and leads to unregulated cholesterol accumulation. Micellar nanolipoblockers (NLBs) consist of alkyl chains and polyethylene glycol on mucic acid. NLBs functionalized with anionic groups inhibit oxLDL uptake via the scavenger receptor A (SR-A). Molecular modeling and docking approaches were used to understand the structure-activity relationship (SAR) between NLBs and SR-A. Six NLB models were docked to the SR-A homology model to investigate charge placement and clustering. NLB models with the most favorable binding energy were also the most effective oxLDL inhibitors in THP-1 macrophages. Mutant SR-A models were generated by replacing charged residues with alanine. All charged residues in the region were necessary, with Lys60, Lys63 and Lys66 having the greatest effect on binding. We hypothesize that structural studies aided by theoretical modeling and docking can be used to design promising NLB candidates with optimal binding properties.
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Details
- Title
- Structure Activity Relations of Nanolipoblockers with the Atherogenic Domain of Human Macrophage Scavenger Receptor A
- Creators
- Nicole Plourde - Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854Sandhya Kortagere - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129William Welsh - Department of Pharmacology, Environmental Bioinformatics & Computational Toxicology Research Center University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, Piscataway, NJ 08854Prabhas Moghe - Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854
- Publication Details
- Biomacromolecules, v 10(6), pp 1381-1391
- Publisher
- American Chemical Society; Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000266860700009
- Scopus ID
- 2-s2.0-67049117928
- Other Identifier
- 991014877871304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Organic
- Polymer Science