Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study
Abstract
:1. Introduction
2. Experimental Procedures
2.1. Materials
2.2. Isolation of Lyso-DGTS
2.3. Synthesis of Lyso-DGTS Derivatives
2.3.1. General Procedure for the Synthesis of (S)-1-Carboxy-3-hydroxy-N,N,N-trimethylpropan-1-aminium (l-Homoserine Betaine) (Scheme 1)
2.3.2. General Procedure for the Synthesis of l-Homoserine Betaine Fatty Acid Ester Derivatives (Scheme 2)
2.3.3. General Procedure for the Synthesis of Amide-Fatty Acid Derivatives
(S)-2-((Tert-butoxycarbonyl) amino)-4-oleylamido butanoic acid (C2) and (S)-2-((Tert-butoxycarbonyl)amino)-4-((5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenamido)butanoic acid (C3) (Scheme 3)
(S)-2-Amino-4-oleylamido Butanoic Acid (C4) and (S)-2-Amino-4-((5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenamido)butanoic Acid (C5) (Scheme 4)
3-(S)-4-((5Z,8Z,11Z,14Z,17Z)-Eicosa-5,8,11,14,17-pentaenamido)-1-methoxy-N,N,N-trimethyl-1-oxobutan-2-aminium (5)) (Scheme 5)
2.4. Chromatography Analysis
2.4.1. HPLC Analysis
2.4.2. LC–MS Analysis
2.5. NMR Analysis
2.5.1. l-Homoserine Betaine
2.5.2. Homoserine Betaine Eicosapentaenoate (2)
2.5.3. Homoserine Betaine Oleate (3)
2.5.4. Homoserine Betaine Palmitate (4)
2.5.5. EPA Amide-Lyso (5)
2.5.6. Oleic Amide-Lyso (6)
2.6. Biological Assays
2.6.1. Effect of the Lipids on rePON1 Lactonase and Arylesterase Activities
2.6.2. Tryptophan (Trp) Fluorescence-Quenching Measurements
2.7. Molecular Docking
2.8. Cu2+-Induced LDL Oxidation
3. Results
3.1. Synthesis of Lyso-DGTS Derivatives
3.2. Effect of Lyso-DGTS Derivatives and Endogenous Analogs on Lactonase Activity of rePON1
3.3. Effect of Lyso-DGTS Derivatives and Endogenous Analogs on Arylesterase Activity of rePON1
3.4. Interaction of Lyso-DGTS Derivatives and Endogenous Analogs with rePON1, Determined via the Trp Fluorescence-Quenching Method
3.5. Interaction between rePON1 and Lyso-DGTS Derivatives and Endogenous Analogs Using Molecular Modeling Calculation
3.6. Effect of rePON1–Lyso-DGTS Derivative and Analog Complexes on Cu2+-Induced LDL Oxidation
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Lag Time | K | % Inhibition |
---|---|---|---|
LDL | 24.22 | 0.04128 | 0 |
1 | 96.8 | 0.0103 | 75.04 |
5 | 99.4 | 0.01006 | 75.62 |
6 | 35.37 | 0.02827 | 31.51 |
2 | 29.37 | 0.03405 | 17.51 |
4 | 25.56 | 0.03913 | 5.20 |
3 | 80.50 | 0.02759 | 33.16 |
Compound | Lag Time | K | % Inhibition |
---|---|---|---|
LDL | 24.08 | 0.04152 | 0 |
1 | 118 | 0.00844 | 79.67 |
5 | 67.87 | 0.01473 | 64.52 |
6 | 29.65 | 0.03373 | 18.76 |
2 | 199 | 0.005013 | 87.9 |
4 | 23.73 | 0.04215 | 0 |
3 | 90.30 | 0.03481 | 16.16 |
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Khattib, A.; Musa, S.; Halabi, M.; Hayek, T.; Khatib, S. Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study. Antioxidants 2022, 11, 2058. https://doi.org/10.3390/antiox11102058
Khattib A, Musa S, Halabi M, Hayek T, Khatib S. Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study. Antioxidants. 2022; 11(10):2058. https://doi.org/10.3390/antiox11102058
Chicago/Turabian StyleKhattib, Ali, Sanaa Musa, Majdi Halabi, Tony Hayek, and Soliman Khatib. 2022. "Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study" Antioxidants 11, no. 10: 2058. https://doi.org/10.3390/antiox11102058
APA StyleKhattib, A., Musa, S., Halabi, M., Hayek, T., & Khatib, S. (2022). Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study. Antioxidants, 11(10), 2058. https://doi.org/10.3390/antiox11102058