Directed evolution as a method to create enantioselective cyclohexanone monooxygenases for catalysis in Baeyer-Villiger reactions.
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Biomedical subjects
Publications and source records attributed to Birgit Brunner.
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[reaction: see text] The epoxide hydrolase (EH) from Aspergillus niger, which shows a selectivity factor of only E = 4.6 in the hydrolytic kinetic resolution of glycidyl phenyl ether, has been subjected to directed evolution for the purpose of enhancing enantioselectivity. After only one round of error-prone polymerase chain reaction (epPCR), enantioselectivity was more than doubled (E = 10.8). The improved mutant enzyme contains three amino acid exchanges, two of which are spatially far from the catalytically active center.
Recalcitrant pruritus is a hallmark of lichen simplex, a localized variant of atopic dermatitis. Acetylcholine has been demonstrated to mediate pruritus in atopic dermatitis. This open pilot study was done to determine the therapeutic effect of blocking acetylcholine release with botulinum toxin A in highly pruritic lichen simplex. Botulinum toxin A (Dysport) was injected intradermally into 5 circumscribed lichenoid lesions in 3 patients suffering from recalcitrant pruritus. No corticosteroids or any other specific topical therapy was administered. Pruritus subsided within 3 to 7 days in all 3 patients. Within 2 to 4 weeks all lesions cleared completely. No recurrences were noted over a 4-month follow-up. In one patient lichen simplex developed on the contralateral shin, which responded equally to a subsequent injection. We concluded that lichen simplex-associated pruritus can be overcome by intradermal botulinum toxin A injection. Acetylcholine appears to be a dominant pruritic mediator in this condition.