Effect of Increase in Orientational Order of Lipid Chains and Head Group Spacing on Non Steroidal Anti-Inflammatory Drug Induced Membrane Fusion
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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Title |
Effect of Increase in Orientational Order of Lipid Chains and Head Group Spacing on Non Steroidal Anti-Inflammatory Drug Induced Membrane Fusion
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Creator |
Mondal Roy, Sutapa
Bansode, Amol S Sarkar, Munna |
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Subject |
Chemistry
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Description |
Membrane fusion is a key event in many biological processes. The fusion process, both in vivo and in vitro, is induced
by different agents which include mainly proteins and peptides. For protein- and peptide-mediated membrane fusion,
conformational reorganization serves as a driving force. Small drug molecules do not share this advantage; hence, drug
induced membrane fusion occurring in absence of any other fusogenic agent and at physiologically relevant
concentration of the drugs is a very rare event. To date, only three drugs, namely, meloxicam (Mx), piroxicam (Px),
and tenoxicam (Tx), belonging to the oxicam group of non steroidal anti-inflammatory drugs (NSAIDs), have been
shown by us to induce fusion at very low drug to lipid ratio without the aid of any other fusogenic agent. In our
continued effort to understand the interplay of different physical and chemical parameters of both the participating
drugs and the membrane on the mechanism of this drug induced membrane fusion, we present here the effect of increase
in orientational order of the lipid chains and increase in head group spacing. This is achieved by studying the effect of low
concentration cholesterol (<10 mol %) at temperatures above the chain-melting transition. Low concentration
cholesterol (<10 mol %), above the gel to fluid transition temperature, is mainly known to increase orientational order
of the lipid chains and increase head group spacing. To isolate the effect of these parameters, small unilameller vesicles
(SUVs) formed by dimyristoylphosphatidylcholine (DMPC) with an average diameter of 50-60 nm were used as simple
model membranes. Fluorescence assays were used to probe the time dependence of lipid mixing, content mixing, and
leakage and also used to determine the partitioning of the drugs in the membrane bilayer. Differential scanning
calorimetry (DSC) was used to study the effect of drugs in the presence of cholesterol on the chain-melting temperature
which reflects the fluidization effect of the hydrophobic tail region of the bilayer. Our results show contradictory effect of
low concentration cholesterol on the fusion induced by the three drugs, which has been explained by parsing the effect of
orientational order and increase in head group spacing on the fusion process.
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Date |
2010
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/1012/1/2_LANG_2010.pdf
Mondal Roy, Sutapa and Bansode, Amol S and Sarkar, Munna (2010) Effect of Increase in Orientational Order of Lipid Chains and Head Group Spacing on Non Steroidal Anti-Inflammatory Drug Induced Membrane Fusion. Langmuir, 26 (24). pp. 18967-18975. |
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Relation |
http://dx.doi.org/10.1021/la103802d
http://www.eprints.iicb.res.in/1012/ |
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