Hydrogen bonds and masking in the sulfhydryl group in proteins

Abstract

Szent-Györgi has shown that the relative amounts of readily titratable (“free”) SH groups vs. those readily titratable only following denaturation (“masked”) varies significantly from normal to cancerous organ tissues. It is therefore important to inquire into the nature of the two forms of protein-borne SH. Of the four suggested mechanisms for the “masking” of protein SH groups toward hydrophilic reagents, namely: (i) sequestration in hydrophobic regions—whether between chain-folds or between agglomerated protein sub-units, (ii) local steric hindrance, (iii) cyclic hydrogen-bonding to local peptide amino acid residues, or (iv) covalent bonding as in thiazoldines; the first mechanism, that of sequestration in hydrophobic regions appears from present evidence to be the most likely cause. Various spectroscopic, reaction rate and entropy arguments are presented and compared which lead to this conclusion. In addition we have calculated the binding energy of the SH group to various sets of lone pair electrons appropriate to N, O, F, P, S, and Cl atoms in molecules. The calculation was made in the configuration interaction of valence orbitals (CIVO) scheme and gave binding energies and interatomic distances in reasonable agreement with available experimental data.