Peptides respresent intriguing materials to achieve sustainable catalytic reactivity that mimic the natural functions of enzymes, but without the limitations of temperature/solvent sensitivity. They could also be applicable to a wide variety of substrates, thus expanding their potential use at different reaction levels ranging from the benchtop to industrial. Unfortunately, significant use of catalytic peptides remains limited due to the general lack of understanding of the fundamental basis of their inherent reactivity. In this contribution, we examine the reactivity of a peptide (termed CPN3) previously isolated with ester hydrolysis reactivity. It is demonstrated that the system is most reactive under slightly basic conditions. While the system is slower than comparable enzymes, it demonstrates significant reactivity across multiple substrates and different reaction conditions that could likely lead to enzymatic denaturation. In addition, key active site residues were identified to begin to elucidate the fundamental basis of the reactivity. Such results could be used to design new sequences with enhanced reactivity under sustainable conditions.