Synthesis of A11^Cys-B11^Cys Disulfide Surrogates of H2 Relaxin through an Intermolecular Native Chemical Ligation-Assisted Diaminodiacid Strategy

We report an intermolecular native chemical ligation-assisted diaminodiacid strategy for the flexible construction of A11(Cys)-B11(Cys) disulfide surrogates of H2 relaxin. The practicality of this strategy was evidenced by the synthesis of four new H2 relaxin analogs, among which H2-2a-B28(Ile) is found to exhibit improved potency, selectivity, and stability compared with native H2 relaxin.