[Reaction of carbodiimide for the introduction of p-bis(2-chloroethyl)amino-L-phenylalanine to lysozyme].
In the synthesis of new prodrugs with inhibitoring action of tumour growth, a new nitrogen mustard derivative was obtained, proceeding of the coupling between an egg-white lysozyme with an antitumor amine nucleophile, the methyl ester of p-bis-(2-chloroethyl)amino-L-phenylalanine (Melphalan), catalyzed by 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide (EDC), at pH 5.0 and room temperature. In that case, the mechanism for the modification isn't selective of Asp101 in lysozyme. As in cases of histamine and D-glucosamine [3], it is evident that Melphalan is one type of amine who doesn't cause a selective modification of Asp101 but causes somewhat random reaction, because Asp101 is modified followed by modifications of other carboxyls. In this case, we suggest that the amine (Melphalan) may also bind to the substrate binding site in competition with EDC. With this type of amine, enzyme-nucleophile interactions predominate, and the selective activation of Asp101 by EDC is reduced to lead a more random reaction.
Smolders
R R
RR
Jacquemotte
F
F
Drouillon
P
P
Legentil
I
I
Pauwels
D
D
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002234:Carbodiimides / Q000032:analysis*; D055598:Chemical Phenomena; D002621:Chemistry; D008558:Melphalan / Q000031:analogs & derivatives*; D009113:Muramidase / Q000032:analysis*
D000970:Antineoplastic Agents; D002234:Carbodiimides; D009113:Muramidase; D008558:Melphalan
Réaction à la carbodiimide visant l'introduction de la p-bis-(2-chloroéthyl)amino-L-phénylalanine sur le lysozyme.