PMID- 17612982 OWN - NLM STAT- MEDLINE DCOM- 20070822 LR - 20091117 IS - 1556-9527 (Print) IS - 1556-9527 (Linking) VI - 26 IP - 2 DP - 2007 TI - The role of non-covalent protein binding in skin sensitisation potency of chemicals. PG - 161-9 AB - Skin sensitisation is a delayed hypersensitivity reaction caused by repeated exposure to common natural and synthetic chemical allergens. It is thought that small chemical sensitisers (haptens) are required to form a strong irreversible bond with a self protein/peptide and generate an immunogenic hapten-protein complex in order to be recognised by the immune system and stimulate T cell proliferation. The sensitisers are usually electrophilic chemicals that are directly reactive with proteins or reactive intermediates (metabolites) of chemically inert compounds (prohaptens). Sensitising chemicals are also capable of weak, non-covalent association with proteins and there is an ongoing debate about the role of weak interactions of chemicals and proteins in the chemistry of allergy. The non-covalent interactions are reversible and thus have a major impact on skin/epidermal bioavailability of chemical/reactive metabolites. We investigated the relationship between the relative level of non-covalent association to a model protein and their relative potencies as determined by the EC3 values in the murine local lymph node assay (LLNA) for a number of chemicals. Using human serum albumin as a model protein, we determined that no observable relationship exists between the two parameters for the chemicals tested. Therefore, at least for this model protein, non-covalent interactions appear not to be a key determinant of allergen potency. FAU - Aleksic, Maja AU - Aleksic M AD - Safety & Environmental Assurance Centre Unilever Colworth, Sharnbrook, Bedfordshire. maja.aleksic@unilever.com FAU - Thain, Emma AU - Thain E FAU - Gutsell, Stephen J AU - Gutsell SJ FAU - Pease, Camilla K AU - Pease CK FAU - Basketter, David A AU - Basketter DA LA - eng PT - Journal Article PL - England TA - Cutan Ocul Toxicol JT - Cutaneous and ocular toxicology JID - 101266892 RN - 0 (Allergens) RN - 0 (Haptens) RN - 0 (Serum Albumin) SB - IM MH - Allergens/*chemistry/*metabolism MH - Chromatography, Affinity MH - Chromatography, High Pressure Liquid MH - Dermatitis, Contact/*metabolism MH - Haptens/metabolism MH - Humans MH - Hypersensitivity, Delayed/*metabolism MH - Local Lymph Node Assay MH - Protein Binding MH - Serum Albumin/immunology MH - Spectrophotometry, Ultraviolet EDAT- 2007/07/07 09:00 MHDA- 2007/08/23 09:00 CRDT- 2007/07/07 09:00 PHST- 2007/07/07 09:00 [pubmed] PHST- 2007/08/23 09:00 [medline] PHST- 2007/07/07 09:00 [entrez] AID - 779876254 [pii] AID - 10.1080/15569520701212282 [doi] PST - ppublish SO - Cutan Ocul Toxicol. 2007;26(2):161-9. doi: 10.1080/15569520701212282.