Computational Insights into the Formation and Structure of S-N Containing Cyclic Peptides

Cyclic peptides areknown to have biologically important rolesand may also be applicable to the pharmaceutical and other industries.Furthermore, thiols and amines, which are found throughout biologicalsystems, can react to form S-N bonds and to date, similar to 100biomolecules containing such a bond have been identified. However,while there are in principle numerous S-N containing peptide-derivedrings possible, only a few are presently known to occur in biochemicalsystems. Density functional theory-based calculations have been usedto consider the formation and structure of S-N containing cyclicpeptides from systematic series of linear peptides in which a cysteinylhas first been oxidized to a sulfenic or sulfonic acid. In addition,the possible effect of the cysteine's vicinal residue on thefree energy of formation has also been considered. In general, whenthe cysteine is first oxidized to a sulfenic acid, only the formationof smaller S-N containing rings is calculated to be exergonicin aqueous solution. In contrast, when the cysteine is first oxidizedto a sulfonic acid, the formation of all rings considered (with oneexception) is calculated to be endergonic in aqueous solution. Thenature of vicinal residue can influence ring formation through stabilizingor destabilizing intramolecular interactions.

Automated summary

Cyclic peptides play important roles in biology and have potential applications in the pharmaceutical and other industries. Although thiols and amines can react to form S-N bonds, only a few cyclic peptides containing such bonds have been identified in biological systems. Density functional theory-based calculations were used to study the formation and structure of S-N containing cyclic peptides from linear peptides. The nature of the vicinal residue of cysteine can affect ring formation through stabilizing or destabilizing intramolecular interactions.