Stability of New Carbapenem DA-1131 to Renal Dipeptidase (Dehydropeptidase I)

The stability of DA-1131 to renal dipeptidase (RDPase) (EC 3.4.13.19) was compared with that of imipenem and meropenem by V(max)/K(m) ratios as an index of the enzyme's preference for substrates. Our results showed a decreasing order of imipenem (6.24), meropenem (2.41), and DA-1131 (1.39). The biochemical evaluation of DA-1131 as the least preferred substrate of RDPase suggests its potential use as a novel β-lactam antibiotic which may be usable without coadministration of RDPase inhibitors once its clinical suitability is proven.

本研究以V(max)/K(m)比值作为酶底物偏好性的评价指标，对比了DA-1131与亚胺培南（imipenem）、美罗培南（meropenem）对肾二肽酶（renal dipeptidase, RDPase，EC 3.4.13.19）的稳定性。实验结果显示，三者的酶底物偏好性由高至低依次为亚胺培南（6.24）、美罗培南（2.41）与DA-1131（1.39）。生化评价结果表明，DA-1131是肾二肽酶偏好性最低的底物，这提示其具备开发为新型β-内酰胺类抗生素（β-lactam antibiotic）的潜力；若其临床适用性得到验证，该化合物有望无需联合使用肾二肽酶抑制剂即可投入临床使用。