Folding and self-assembling with beta-oligomers based on (1R,2S)-2-aminocyclobutane-1-carboxylic acid.
Improved methodologies are provided to synthesize (1R,2S)-2-aminocyclobutane-1-carboxylic acid derivatives and their incorporation into beta-peptides of 2-8 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.
Torres
Elisabeth
E
Departament de Química, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
Gorrea
Esther
E
Burusco
Kepa K
KK
Da Silva
Eric
E
Nolis
Pau
P
Rúa
Federico
F
Boussert
Stéphanie
S
Díez-Pérez
Ismael
I
Dannenberg
Samantha
S
Izquierdo
Sandra
S
Giralt
Ernest
E
Jaime
Carlos
C
Branchadell
Vicenç
V
Ortuño
Rosa M
RM
D000598:Amino Acids, Cyclic / Q000737:chemistry*; D002942:Circular Dichroism; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008853:Microscopy; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D012996:Solutions; D013237:Stereoisomerism
C541323:2-aminocyclobutane-1-carboxylic acid; D000598:Amino Acids, Cyclic; D009842:Oligopeptides; D012996:Solutions