Dataset Information

Stereoselectivity of isoflurane in adhesion molecule leukocyte function-associated antigen-1.

ABSTRACT:

Background

Isoflurane in clinical use is a racemate of S- and R-isoflurane. Previous studies have demonstrated that the effects of S-isoflurane on relevant anesthetic targets might be modestly stronger (less than 2-fold) than R-isoflurane. The X-ray crystallographic structure of the immunological target, leukocyte function-associated antigen-1 (LFA-1) with racemic isoflurane suggested that only S-isoflurane bound specifically to this protein. If so, the use of specific isoflurane enantiomers may have advantage in the surgical settings where a wide range of inflammatory responses is expected to occur. Here, we have further tested the hypothesis that isoflurane enantioselectivity is apparent in solution binding and functional studies.

Methods

First, binding of isoflurane enantiomers to LFA-1 was studied using 1-aminoanthracene (1-AMA) displacement assays. The binding site of each enantiomer on LFA-1 was studied using the docking program GLIDE. Functional studies employed the flow-cytometry based ICAM binding assay.

Results

Both enantiomers decreased 1-AMA fluorescence signal (at 520 nm), indicating that both competed with 1-AMA and bound to the ?L I domain. The docking simulation demonstrated that both enantiomers bound to the LFA-1 "lovastatin site." ICAM binding assays showed that S-isoflurane inhibited more potently than R-isoflurane, consistent with the result of 1-AMA competition assay.

Conclusions

In contrast with the x-ray crystallography, both enantiomers bound to and inhibited LFA-1. S-isoflurane showed slight preference over R-isoflurane.

SUBMITTER: Bu W

PROVIDER: S-EPMC4011845 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Stereoselectivity of isoflurane in adhesion molecule leukocyte function-associated antigen-1.

Bu Weiming W Pereira Luis M LM Eckenhoff Roderic G RG Yuki Koichi K

PloS one 20140506 5

<h4>Background</h4>Isoflurane in clinical use is a racemate of S- and R-isoflurane. Previous studies have demonstrated that the effects of S-isoflurane on relevant anesthetic targets might be modestly stronger (less than 2-fold) than R-isoflurane. The X-ray crystallographic structure of the immunological target, leukocyte function-associated antigen-1 (LFA-1) with racemic isoflurane suggested that only S-isoflurane bound specifically to this protein. If so, the use of specific isoflurane enantio ...[more]

PMID: 24801074

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Dataset Information

Stereoselectivity of isoflurane in adhesion molecule leukocyte function-associated antigen-1.

Background

Methods

Results

Conclusions

Publications

Stereoselectivity of isoflurane in adhesion molecule leukocyte function-associated antigen-1.

Similar Datasets

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