Folding and self-assembling with beta-oligomers based on (1R,2S)-2-aminocyclobutane-1-carboxylic acid

ELIZABETH TORRES; ESTHER GORREA; KEPA K. BURUSCO; ERIC DA SILVA; PAU NOLIS; FEDERICO RÚA; STÉPHANIE BOUSSERT; ISMAEL DÍEZ-PÉREZ; SAMANTHA DANNENBERG; SANDRA IZQUIERDO; ERNEST GIRALT; VICENÇ BRANCHADELL; ROSA MARÍA ORTUÑO

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2010 vol. 8 p. 564 - 575

1477-0520

Improved methodologies are provided to synthesize (1R,2S)-2-aminocyclobutane-1-carboxylic acid derivatives and their incorporation into beta-peptides of 278 residues bearing different N-protecting groups. The conformational analysis of these oligomers has been carried out by using experimental techniques along with theoretical calculations. This study shows that these oligomers adopt preferentially a strand-type conformation in solution induced by the formation of intra-residue six-membered hydrogen-bonded rings, affording cis-fused [4.2.0]octane structural units that confer high rigidity on these beta-peptides. Moreover, all of them are prone to self-assemble producing nano-sized fibres, as evidenced by TEM, AFM and SPFM, and, in some instances, they also form gels. These techniques and molecular modelling allowed us to suggest an aggregation model for the assembly structures in which a parallel molecular-arrangement is preferred and the conformation is similar to that observed in solution. According to this model, both hydrogen-bonding and hydrophobic interactions would account for formation of the assemblies.