The Role of the Internal Cross-Link in Oxytocin. Preparation of Mercury Mercaptide Oxytocin Derivatives

The disulfide bond of oxytocin was reduced using an insoluble reducing reagent, dihydrolipoyl attached to polyacrylamide P-6. The sulfhydryl groups thus formed were bridged by bivalent mercury ion with the formation of an S-Hg-S bridge. The monomeric product obtained was shown to be homogeneous and contained one mercury atom per peptide molecule. Further addition of mercury ions led to the formation of a dimercurated open-chain derivative. The mercuration had a marked effect on the ultraviolet and circular dichroic spectral features of these derivatives in comparison with oxytocin. The tryosine's fluorescence intensity of mono-and dimercurated oxytocin derivatives was quenched in comparison with that of oxytocin and oxytoceine, respectively. The mercury-oxytocin derivatives were found to have negligible biological activity as muscular-contracting agents of isolated rat uteri. Elongation of the internal crosslink of oxytocin by 3 Å, thus dramatically affects the biological activity of the hormone, which is intimately connected with the native conformation of the peptide.