Mechanism of the antigen formation of carvone and related alpha, beta-unsaturated ketones
(2001) In Contact Dermatitis 44(6). p.347-356- Abstract
- In the present study, the mechanism for the antigen formation of alpha, beta-unsaturated ketones was investigated. A series of analogues of carvone ((5R)-5-isopropenyl-2-methyl-2-cyclohexenone) with altered chemical reactivity and with retained overall structure or with retained reactivity and altered three-dimensional structure were synthesized. These analogues were tested for cross-reactivity in carvone-sensitized animals. Cross-reactivity was observed for analogue 3 ((5R)-5-isopropyl-2-methyl-2-cyclohexen-1-one). No cross-reactions were observed for analogues 1 ((2R,5R)-5-isopropenyl-2-methyl cyclohexanone) and 4 ((5R)-2,3-dimethyl-5-isopropenyl-2-cyclohexene-1-one). Both those compounds also failed to induce sensitization. These... (More)
- In the present study, the mechanism for the antigen formation of alpha, beta-unsaturated ketones was investigated. A series of analogues of carvone ((5R)-5-isopropenyl-2-methyl-2-cyclohexenone) with altered chemical reactivity and with retained overall structure or with retained reactivity and altered three-dimensional structure were synthesized. These analogues were tested for cross-reactivity in carvone-sensitized animals. Cross-reactivity was observed for analogue 3 ((5R)-5-isopropyl-2-methyl-2-cyclohexen-1-one). No cross-reactions were observed for analogues 1 ((2R,5R)-5-isopropenyl-2-methyl cyclohexanone) and 4 ((5R)-2,3-dimethyl-5-isopropenyl-2-cyclohexene-1-one). Both those compounds also failed to induce sensitization. These findings demonstrate that alpha, beta-unsaturated ketones form antigens after a nucleophilic attack at the beta-carbon with soft nucleophiles such as thiol in cysteine and not with the formation of a Schiff's base after a nucleophilic attack at the carbonyl carbon with nitrogen nucleophiles. Furthermore, no cross-reactivity was observed between R- and S-carvone indicating the importance of the 3-dimensional structure of haptens (and antigens) in T-cell recognition. The analogues were also tested for cross-reactivity on patients allergic to carvone. The results from the animal study were confirmed. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1121652
- author
- Nilsson, Anna-Malin ; Gafvert, Elisabeth ; Salvador, Lourdes ; Luthman, Kristina ; Bruze, Magnus LU ; Gruvberger, Birgitta LU ; Nilsson, J. Lars G. and Karlberg, Ann-Therese
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- allergic contact dermatitis, carvone, enantiospecificity, Michael addition, Schiff's base, structure-activity relationship, α, β-unsaturated ketones
- in
- Contact Dermatitis
- volume
- 44
- issue
- 6
- pages
- 347 - 356
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:11380545
- scopus:0034991709
- ISSN
- 0105-1873
- DOI
- 10.1034/j.1600-0536.2001.044006347.x
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Occupational and Environmental Dermatology Unit (013241310), Pediatrics/Urology/Gynecology/Endocrinology (013240400)
- id
- 34ae8d09-c6eb-41a8-bca2-e9414ee645a4 (old id 1121652)
- date added to LUP
- 2016-04-01 12:35:30
- date last changed
- 2022-05-26 08:43:51
@article{34ae8d09-c6eb-41a8-bca2-e9414ee645a4,
abstract = {{In the present study, the mechanism for the antigen formation of alpha, beta-unsaturated ketones was investigated. A series of analogues of carvone ((5R)-5-isopropenyl-2-methyl-2-cyclohexenone) with altered chemical reactivity and with retained overall structure or with retained reactivity and altered three-dimensional structure were synthesized. These analogues were tested for cross-reactivity in carvone-sensitized animals. Cross-reactivity was observed for analogue 3 ((5R)-5-isopropyl-2-methyl-2-cyclohexen-1-one). No cross-reactions were observed for analogues 1 ((2R,5R)-5-isopropenyl-2-methyl cyclohexanone) and 4 ((5R)-2,3-dimethyl-5-isopropenyl-2-cyclohexene-1-one). Both those compounds also failed to induce sensitization. These findings demonstrate that alpha, beta-unsaturated ketones form antigens after a nucleophilic attack at the beta-carbon with soft nucleophiles such as thiol in cysteine and not with the formation of a Schiff's base after a nucleophilic attack at the carbonyl carbon with nitrogen nucleophiles. Furthermore, no cross-reactivity was observed between R- and S-carvone indicating the importance of the 3-dimensional structure of haptens (and antigens) in T-cell recognition. The analogues were also tested for cross-reactivity on patients allergic to carvone. The results from the animal study were confirmed.}},
author = {{Nilsson, Anna-Malin and Gafvert, Elisabeth and Salvador, Lourdes and Luthman, Kristina and Bruze, Magnus and Gruvberger, Birgitta and Nilsson, J. Lars G. and Karlberg, Ann-Therese}},
issn = {{0105-1873}},
keywords = {{allergic contact dermatitis; carvone; enantiospecificity; Michael addition; Schiff's base; structure-activity relationship; α; β-unsaturated ketones}},
language = {{eng}},
number = {{6}},
pages = {{347--356}},
publisher = {{Wiley-Blackwell}},
series = {{Contact Dermatitis}},
title = {{Mechanism of the antigen formation of carvone and related alpha, beta-unsaturated ketones}},
url = {{http://dx.doi.org/10.1034/j.1600-0536.2001.044006347.x}},
doi = {{10.1034/j.1600-0536.2001.044006347.x}},
volume = {{44}},
year = {{2001}},
}