Disulfide Bond Based Self-Assembly of Peptides Leading To Spheroidal Cyclic Trimers

Abstract

Oxidation in the presence of TFE of several [19]- or [20]-peptides with two cysteine residues in positions i, i+17 and with two serine residues at positions i+8 and i+9 leads to the spontaneous formation, in high yields, of cyclic disulfide bonded trimers in which two of the chains are parallel and the third one is antiparallel. The serine residues in the center of the sequence are a necessary requirement for trimer formation which results from destabilization of the helical parallel cyclic dimer.

The cyclic structure is incompatible with a cylindrical coiled-coil helix bundle but is consistent with a quasi-spherical topology in which individual peptides, in an α-helical conformation, occupy non-intersecting edges of an octahedron and the disulfide bonds complete the cyclic structure along three of the remaining edges.

The easy synthetic access to this peptide scaffold opens the way to a number of possible applications,includingaster molecules, dendrimer coresor immunological carriers. By using peptide mixtures, trimer libraries can be prepared. Disulfide bond scrambling under thermodynamic control alsoopens the way to the preparation of virtual trimer libraries.