Effects of the alternating backbone configuration on the secondary structure and self-assembly of beta-peptides.
Heterochiral homo-oligomers with alternating backbone configurations were constructed by using the different enantiomers of the cis- and trans-2-aminocyclopentanecarboxylic acid (ACPC) monomers. Molecular modeling and the spectroscopic techniques (NMR, ECD, and VCD) unequivocally proved that the alternating heterochiral cis-ACPC sequences form an H10/12 helix, where extra stabilization can be achieved via the cyclic side chains. The ECD and TEM measurements, together with molecular modeling, revealed that the alternating heterochiral trans-ACPC oligomers tend to attain a polar-strand secondary structure in solution, which can self-assemble into nanostructured fibrils. The observations indicate that coverage of all the possible secondary structures (various helix types and strand-mimicking conformations) can be attained with the help of cyclic beta-amino acid diastereomers. A relationship has been established between the backbone chirality pattern and the prevailing secondary structure, which underlines the role of stereochemical control in the beta-peptide secondary structure design and may contribute to future biological applications.
Martinek
Tamás A
TA
Institute of Pharmaceutical Chemistry and Department of Medical Chemistry, University of Szeged, H-6701 Szeged, POB 427, Hungary.
Mándity
István M
IM
Fülöp
Lívia
L
Tóth
Gábor K
GK
Vass
Elemér
E
Hollósi
Miklós
M
Forró
Eniko
E
Fülöp
Ferenc
F
D000595:Amino Acid Sequence; D000598:Amino Acids, Cyclic / Q000737:chemistry*; D002942:Circular Dichroism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry; D013237:Stereoisomerism
D000598:Amino Acids, Cyclic; D010455:Peptides; D012996:Solutions; D003515:Cycloleucine; C065594:cispentacin