Hormone-receptor interactions. Synthesis and conformational study of cyclo-L-cystathionine.

The purpose of this work was to see whether the replacement of a sulfur atom in a cystine disulfide bridge by a methylene group is an only superficial ‘isosteric’ substitution, i.e. with regard to size, hydrophobia, bond angles, etc., or whether it would also encompass such parameters as preferred conformations in solution (M- or P-helicity of the bridge). The methods involved the synthesis of a model compound, cyclo-L -cystathionine (cyclo-L -carbacystine), and its investigation by ¹H- and ¹³C-NMR. It is concluded that the conformations of the CH₂(β)? CH₂(γ)? S? CH₂(β') bridge, and of the diketopiperazine ring are closely similar to the analogous elements in cyclo-L -cystine (DMSO as solvent). This knowledge might help to explain the fact that carba analogs of heterodetic-cyclic polypeptide hormones are often biologically very active.