Aziridine-2-carboxylic acid. A reactive amino acid unit for a new class of cysteine proteinase inhibitors.
The three-membered ring of aziridine-2-carboxylic acid, which is susceptible to opening by nucleophiles, has been analyzed as a potential useful handle for the design of specific irreversible inhibitors of cysteine proteinases. For this thiol-reactive amino acid, an imino analogue of proline, a second-order rate constant of 17.07 M-1.s-1 for inactivation of papain was determined. Thus, the aziridine moiety proved to be remarkably more reactive than activated double bonds, e.g. N-ethylmaleimide, or halides such as alpha-iodopropionic acid or chloroacetic acid. Since it does not alkylate histidine under conditions in which quantitative alkylation occurs with N-ethyl-maleimide, it could represent an interesting reactive amino acid unit for the synthesis of a new class of irreversible inhibitors, at least in terms of specificity of the chemical reaction involved in the inactivation process.
Moroder
L
L
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Musiol
H J
HJ
Scharf
R
R
Morodor
L
L
D001388:Aziridines / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D010206:Papain / Q000037:antagonists & inhibitors*
D001388:Aziridines; C073440:aziridine-2-carboxylic acid; D010206:Papain