Exploring the interest of 1, 2-dithiolane ring system in peptide chemistry. Synthesis of a chemotactic tripeptide and x-ray crystal structure of a 4-amino-1, 2-dithiolane-4-carboxylic acid derivative

1,2-dithiolanes (five-membered cyclic disulfides) represent an emerging class of heterocyclic compounds due to their relevant biological functions and specific chemical reactivity. However, despite the extensive research centered on lipoic acid and its analogues, only very few data are at the present available on peptides containing this ring system. Due to an interplay of conformational and electronic effects, connected with the size of the ring, the chemical reactivity of 1,2-dithiolanes is well distinct from that of linear and related cyclic disulfides, and represents the key structural feature on which the activity of relevant biomolecules, such as lipoic acid, is based. In the context of C-alpha tetrasubstituted aminoacids, we have prepared the new 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) residue and we have inserted it into the chemotactic peptide For-Met-Leu-Phe-OMe (fMLP-OMe), obtaining in this way the analog For-Met-Adt-Phe-OMe (fMAP-OMe). The biological activity of the Adt containing tripeptide was determined on human neutrophils and compared with that of the bioactive prototype fMLP-OMe. fMAP-OMe shows a lower potency in inducing directed migration (chemotaxis), but comparable activity in lysozyme release and superoxide anion production.