Solid state structures and solution phase self-assembly of clicked mannosylated diketopiperazines

Abstract

Peptides and peptide conjugates elicit considerable interest for diverse applications ranging from materials science to biology, for unique molecular recognition properties, and for solution phase self-assembly. Diketopiperazines (DKPs) are an important class of cyclic scaffolds, which offer a useful platform for studying self-organization and several biological activities. This paper presents synthesis of unsymmetrical DKPs containing the aromatic amino acid tryptophan, crystallographic signatures, and solution-phase self-assembly. These DKPs were synthesized via an intramolecular reaction using dicyclohexylcarbodiimide as a coupling agent, followed by a Huisgen aza-alkyne click reaction to conjugate carbohydrate residues with the DKP scaffold. These conjugates were studied with the help of single crystal analysis, NMR spectroscopy and scanning electron microscopy (SEM). DKPs 6a and 8a did not reveal the conventional ‘tape-like’ motif in the solid state as compared to their symmetrical analogues, but exhibited emergence of spherical structures in solution.