Enantioselective immunorecognition of protein modification with optically active ibuprofen using polyclonal antibody

Ito, Hiromi; Ishiwata, Shunji; Kosaka, Takashi; Nakashima, R.; Takeshita, Harunori; Negoro, Sakiko; Maeda, Masako; Ikegawa, Shigeo

doi:10.1016/j.jchromb.2004.01.040

Cited by 7 publications

(6 citation statements)

References 22 publications

(23 reference statements)

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“…Enantioselective recognition of ( S )-ibuprofen protein adducts has been demonstrated by using a polyclonal antibody. It was implied that the adduction was caused ultimately by the AG of ( S )-ibuprofen 10 , mediated via thioesters . This selectivity has also been exploited in an immunoaffinity extraction process .…”

Section: Interaction Of Acyl Glucuronides With Biomoleculesmentioning

confidence: 99%

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Acyl Glucuronides: Biological Activity, Chemical Reactivity, and Chemical Synthesis

et al. 2006

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which after mutarotation at C(1) may transfer the acyl group back to the 1R-OH. This has been conclusively demonstrated by NMR spectroscopy. 14,30 Other rearranged forms of AGs are also known. When the Mitsunobu synthesis 32 (see Synthesis) is used, lactones of type 5 are byproducts, sometimes in appreciable yields. The mechanism of formation is not clear but presumably involves cyclization of the first-formed intermediate ester. If there were an in vivo route to such lactones via free carboxyl acyl glucuronides, they would doubtless be potent acylating agents, transferring in this case the sugar along with the acyl residue.Concerning 1β-AGs of benzoic acids, the chemical stability/ reactivity may be predicted with some confidence by a Hammett correlation, 33 as discussed in detail later (NMR section). Some preliminary studies have been carried out on the computational chemistry modeling of the relative stabilities of the isomers of the AGs of 2-, 3-, and 4-trifluoromethylbenzoic acids. 34 For nonarylcarboxylic acids, the structure-reactivity is more complex. Certainly branching at the R-carbon is a factor leading to increased stability; thus the AGs of gemfibrozil 6, 35 clofibric acid 7 36 and valproic acid 8, 37 all doubly R-substituted, display long half-lives (from about 6-70 h in pH 7.4 buffer 37 ).AGs derived from NSAIDs such as naproxen 9 and ibuprofen 10 generally have half-lives from 1 to 4 h under the same conditions. 38 In such compounds, an additional complication is the different rates of rearrangement of the (R)-and (S)-AG diastereoisomers. In the case of 2-phenylpropanoic acid itself 11, 38 this rate was found to be about twice as fast for the (2R)as for the (2S)-AG epimer, and this ratio is typical of the 2-aryl propanoate class. Scheme 2. Possible Fates of AGs Scheme 3. Reactivity of Acyl Glucuronides a a Clearly the rearrangement (pathway 2) requires migration of the acyl group at least as far as O(3).

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Section: Interaction Of Acyl Glucuronides With Biomoleculesmentioning

confidence: 99%

“…It was implied that the adduction was caused ultimately by the AG of (S)-ibuprofen 10, mediated via thioesters. 61 This selectivity has also been exploited in an immunoaffinity extraction process. 62 A different kind of selectivity may be seen where the positional AG isomers are relatively long-lived.…”

Section: Interaction Of Acyl Glucuronides With Biomoleculesmentioning

confidence: 99%

Acyl Glucuronides: Biological Activity, Chemical Reactivity, and Chemical Synthesis

et al. 2006

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“…Some efforts have been made to develop enantioselective antibodies to detect protein adducts modified by chiral ligands, such as ibuprofen. 36 The present study is a follow-up of our earlier antibody work designed to detect protein SO (racemic) adducts.…”

Section: Resultsmentioning

confidence: 97%

Development of Enantioselective Polyclonal Antibodies to Detect Styrene Oxide Protein Adducts

et al. 2009

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Styrene has been reported to be pneumotoxic and hepatotoxic in humans and animals. Styrene oxide, a major reactive metabolite of styrene, has been found to form covalent binding with proteins, such as albumin and hemoglobin. Styrene oxide has two optical isomers and it was reported that the (R)-enantiomer was more toxic than the (S)-enantiomer. The purpose of this study was to develop polyclonal antibodies that can stereoselectively recognize proteins modified by styrene oxide enantiomers at cysteine residues. Immunogens were prepared by alkylation of thiolated keyhole limpet hemocyanin (KLH) with styrene oxide enantiomers. Polyclonal antibodies were raised by immunization of rabbits with the chiral immunogens. Titration tests showed all six rabbits generated high titers of antisera that recognize (R)- or (S)-coating antigens accordingly. No cross-reaction was observed toward the carrier protein (BSA). All three rabbits immunized with (R)-immunogen produced antibodies that show enantioselectivity to the corresponding antigen, while only one among the three rabbits immunized with (S)-immunogen generated antibodies with enantioselectivity of the recognition. The enantioselectivity was also observed in competitive ELISA and immunoblot analysis. Additionally, competitive ELISA tests showed that the immunorecognition required the hydroxyl group of the haptens. Immunoblot analysis demonstrated that the immunorecognition depended on the amount of protein adducts blotted and hapten loading in protein adducts. In summary, we successfully developed polyclonal antibodies to stereoselectively detect protein adducts modified by styrene oxide enantiomers.

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“…7,19 However, the prepared enantioselective antibody oen had crossreactivity to distomer, and it indicated that the antibody could still recognize distomer in some extent. [20][21][22] For example, the Sibuprofen antibody still had more than 50% cross-reactivity to the R-enantiomer. 20 Enantioselective antibodies had the ability to recognize the distomer, which would restrict the application of antibodies in the eld of chiral drug separation and detection.…”

Section: Introductionmentioning

confidence: 99%

“…[20][21][22] For example, the Sibuprofen antibody still had more than 50% cross-reactivity to the R-enantiomer. 20 Enantioselective antibodies had the ability to recognize the distomer, which would restrict the application of antibodies in the eld of chiral drug separation and detection. It would cause false positives in analytical methods and decrease separation efficiency of separation methods.…”

Section: Introductionmentioning

confidence: 99%

Conformational adaptability determining antibody recognition to distomer: structure analysis of enantioselective antibody against chiral drug gatifloxacin

et al. 2021

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Enantioselective immunorecognition of protein modification with optically active ibuprofen using polyclonal antibody

Cited by 7 publications

References 22 publications

Acyl Glucuronides: Biological Activity, Chemical Reactivity, and Chemical Synthesis

Acyl Glucuronides: Biological Activity, Chemical Reactivity, and Chemical Synthesis

Development of Enantioselective Polyclonal Antibodies to Detect Styrene Oxide Protein Adducts

Conformational adaptability determining antibody recognition to distomer: structure analysis of enantioselective antibody against chiral drug gatifloxacin

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