Generation of two isomers with the same disulfide connectivity during disulfide bond formation of human uroguanylin

✍ Scribed by Naoyoshi Chino; Shigeru Kubo; Mikiya Miyazato; Masamitsu Nakazato; Kenji Kangawa; Shumpei Sakakibara

• Book ID: 104634223
• Publisher: Springer Netherlands
• Year: 1996
• Tongue: English
• Weight: 473 KB
• Volume: 3
• Category: Article
• ISSN: 1573-3149
• DOI: 10.1007/bf00131085

✦ Synopsis

In a two-step selective disulfide-bond-forming reaction of human uroguanylin, a 16-residue peptide with two intramolecular disulfide bonds, two compounds (I and II) were formed, which could be detected by RP-HPLC after the second disulfide-bond-forming reaction and were isolated as single entities. Their primary structures, molecular weights, and disulfide connectivities proved to be identical, but their optical rotation values were different, suggesting that they are topological isomers. Only compound 1 was found to increase the cGMP levels in cultured T84 cells significantly. The ratio of these compounds was affected by the order of the disulfide-bond-forming reactions, but not by the solvent used. The presence of a carboxyl-terminal leucine residue seems to be crucial for stabilizing the conformation of the two isomers.