10.1021/acs.orglett.6b02751.s001 Xu Yang Xu Yang Vasily Gelfanov Vasily Gelfanov Fa Liu Fa Liu Richard DiMarchi Richard DiMarchi Synthetic Route to Human Relaxin‑2 via Iodine-Free Sequential Disulfide Bond Formation American Chemical Society 2016 Relaxin insertion relaxin B-chain assembly iodine Synthetic Route absence sequential disulfide bond formation process thiol B chain penicillin G acylase-labile Phacm combination solubility activator Iodine-Free Sequential Disulfide Bond Formation relaxin -2 isoacyl dipeptide segments resin cysteine protection Human challenge 2016-10-18 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Synthetic_Route_to_Human_Relaxin_2_via_Iodine-Free_Sequential_Disulfide_Bond_Formation/4039806 A new synthetic route to human relaxin-2 has been established through a sequential disulfide bond formation process in the absence of iodine. It is enabled by a combination of cysteine protection with penicillin G acylase-labile Phacm and a newly identified thiol activator bis­(5-(2-methoxyethoxy)-2-pyrimidinyl disulfide. The long-standing challenges in relaxin B-chain assembly and its poor solubility have been solved by the insertion of two isoacyl dipeptide segments. The overall yield was 25% from the B chain and 5.8% from the B-chain starting resin.