In di-isopropylmaleamic acids derived from β-amino-acids (i) the rate constant for hydrolysis of the unactivated amide group is comparable with Kcat for pepsin hydrolysing good syntheic substrates; (ii) a neighbouring carboxy-group participates as a nucleophilic catalyst, but requires a specific structural relationship with the amide group to reach high efficiency; (iii) there is a requirement for a second carboxy-group, also in a special structural relationship with the amide group, but this time in the ionised form, for full catalytic efficiency to be maintained. Remarkably, the ionised carboxy-group acts as a general base to catalyse the interconversion of neutral and zwitterionic forms of the tetrahedral carbinolamine intermediate, a reaction which is catalysed by external general acids. As a result we have developed a system showing a bell-shaped pH–rate profile for hydrolysis, of the sort shown by many enzyme-catalysed reactions, and for the same reasons.