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Mechanism of the antigen formation of carvone and related alpha, beta-unsaturated ketones

Nilsson, Anna-Malin; Gafvert, Elisabeth; Salvador, Lourdes; Luthman, Kristina; Bruze, Magnus LU ; Gruvberger, Birgitta LU ; Nilsson, J. Lars G. and Karlberg, Ann-Therese (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:
author
organization
publishing date
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
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:11380545
  • scopus:0034991709
ISSN
0105-1873
DOI
10.1034/j.1600-0536.2001.044006347.x
language
English
LU publication?
yes
id
34ae8d09-c6eb-41a8-bca2-e9414ee645a4 (old id 1121652)
date added to LUP
2008-07-08 10:34:09
date last changed
2018-01-07 06:23:40
@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},
  keyword      = {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    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  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},
  volume       = {44},
  year         = {2001},
}