Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids

Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids

Bibliographic Details
Main Author: Choi, Jaewoo
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2010
Subjects:
Chemistry
Phosphatidylserines
lysophosphatidylcholine
nonenzymatic spontaneous deacylation
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1277142986
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case12771429862021-08-03T05:33:33Z Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids Choi, Jaewoo Chemistry Phosphatidylserines lysophosphatidylcholine nonenzymatic spontaneous deacylation <p>Identification of an interaction between the scavenger receptor CD36 and oxidized phosphatidylserines (oxPSs) can offer insight into the mechanism of the externalization of PSs which is essential for triggering anti-inflammatory responses in macrophages. To determine relative affinities for CD36, a diverse family of oxidatively-truncated PSs possessing various oxidatively truncated <i>sn</i>-2 acyl groups, i.e.,ω-carboxylalkanoyl, ω-oxoalkanoyl, and γ-keto-α,β-unsaturated carbonyl, were efficiently synthesized (Chapter 2).</p> <p>Elevated levels of sn-2-lysophosphatidylcholine (lysoPC) have been linked to cardiovascular complications, and some oxidized phosphatidylcholines undergo facile spontaneous non-enzymatic deacylation. This leads to the expectation that lipase-inhibiting drugs cannot completely prevent the release of lysoPC from oxidatively damaged phospholipids (Chapter 4). The decomposition of 4-hydroxy-7-oxohept-5-enoic acid ester of 2-lyso-phosphatidylcholine (HOHA-PC, t<sub>1/2</sub> = 30 min) was more rapid than that of 5-hydroxy-8-oxo-6-octenoic acid ester of 2-lyso-phosphatidylcholine (HOOA-PC, t<sub>1/2</sub> = 2 h) under neutral conditions (pH 7.4). In contrast, after 24 h, the decomposition of 9-hydroxy-12-oxododec-10-enoic acid ester of 2-lyso-phosphatidylcholine (HODA-PC), for which intramolecular transesterification is disfavorable since it requires formation of a 10-membered lactone, was only 50% complete. The decomposition of HOHA-PC to generate, <i>inter alia</i>, lysoPC occurs more readily (t<sub>1/2</sub> = 30 min) under near-neutral conditions (pH 7.4) as compared to weakly acidic (t<sub>1/2</sub> = 3 h at pH 6) or moderately acidic conditions (t<sub>1/2</sub> = 6 h at pH 4). To investigate non-enzymatic spontaneous deacylation of oxidized PCs, efficient new syntheses of HOHA, HOOA and HODA-PCs were devised (Chapter 3).</p> <p>We postulated that 4-hydroxydocosahexaenoyl-phosphatidylcholine (4-HDHE-PC) was not detected previously in the singlet oxygen reaction product mixture (after reduction) because it is unstable owing to the proximity of the hydroxyl group to the ester carbonyl (Chapter 5). To support hypothesis, we demonstrated that 4-HDHE-PC undergoes spontaneous deacylation to form 4-hydroxydocosahexaenoic acid lactone and lysoPC. The formation of lysoPC and lactonized by-product was confirmed by LC/MS/MS. The rate of 4-HDHE-PC decomposition is affected by the reaction environment: deacylation was faster in homogeneous solution (t<sub>1/2</sub> = 8 h at pH 7.4), a relatively more aqueous environment, than in heterogeneous solution (liposome, t<sub>1/2</sub> = 15 h), where the oxidized acyl chain is buried in a relatively more hydrophobic environment.</p> 2010-07-30 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1277142986 http://rave.ohiolink.edu/etdc/view?acc_num=case1277142986 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Chemistry
Phosphatidylserines
lysophosphatidylcholine
nonenzymatic spontaneous deacylation
spellingShingle Chemistry
Phosphatidylserines
lysophosphatidylcholine
nonenzymatic spontaneous deacylation
Choi, Jaewoo
Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids
author Choi, Jaewoo
author_facet Choi, Jaewoo
author_sort Choi, Jaewoo
title Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids
title_short Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids
title_full Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids
title_fullStr Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids
title_full_unstemmed Part I: Total Syntheses of Novel Oxidatively-truncated Phosphatidylserines Part II: A Nonenzymatic Route to Lysophosphatidylcholine: Spontaneous Deacylation of Oxidatively Damaged Phospholipids
title_sort part i: total syntheses of novel oxidatively-truncated phosphatidylserines part ii: a nonenzymatic route to lysophosphatidylcholine: spontaneous deacylation of oxidatively damaged phospholipids
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2010
url http://rave.ohiolink.edu/etdc/view?acc_num=case1277142986
work_keys_str_mv AT choijaewoo partitotalsynthesesofnoveloxidativelytruncatedphosphatidylserinespartiianonenzymaticroutetolysophosphatidylcholinespontaneousdeacylationofoxidativelydamagedphospholipids
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