Structure-activity relations of nanolipoblockers with the atherogenic domain of human macrophage scavenger receptor A.
Structure-activity relations of nanolipoblockers with the atherogenic domain of human macrophage scavenger receptor A.
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DOI：
10.1021/bm8014522
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发表时间：
2009-06-08
影响因子：
6.2
通讯作者：
Moghe, Prabhas V.
中科院分区：
文献类型：
--
作者：
Plourde, Nicole M.;Kortagere, Sandhya;Welsh, William;Moghe, Prabhas V.
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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影响因子：
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Chnari, E;Lari, HB;Moghe, PV
通讯作者：
Moghe, PV
影响因子：
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GO, N
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