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Pivalase Catalytic Antibodies: Towards Abzymatic Activation of Prodrugs
Author(s) -
Bensel Nicolas,
Reymond Martine T.,
Reymond JeanLouis
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20011105)7:21<4604::aid-chem4604>3.0.co;2-z
Subject(s) - phosphonate , hapten , prodrug , chemistry , catalysis , benzimidazole , substrate (aquarium) , umbelliferone , antibody , combinatorial chemistry , stereochemistry , organic chemistry , biochemistry , coumarin , medicine , biology , immunology , ecology
Screening of monoclonal‐antibody libraries generated against the tert ‐butyl phosphonate hapten 2 and the chloromethyl phosphonate hapten 3 with pivaloyloxymethyl‐umbelliferone 1 as a fluorogenic substrate led to the isolation of eleven catalytic antibodies with rate accelerations around k cat / k uncat =10 3 . The antibodies are not inhibited by the product and accept different acyloxymethyl derivatives of acidic phenols as substrates. The highest activity was found for the bulky, chemically less‐reactive pivaloyloxymethyl group; there is no activity with acetoxymethyl or acetyl esters. This difference might reflect the preference of the immune system for hydrophobic interactions in binding and catalysis. Pivalase catalytic antibodies might be useful for activating orally available pivaloyloxymethyl prodrugs.