Synthesis and Structural Characterization of Helix-Forming â-Peptides: trans-2-Aminocyclopentanecarboxylic Acid Oligomers
Daniel H. Appella, Laurie A. Christianson, Daniel A. Klein, Michele R. Richards, Douglas R. Powell, Samuel H. Gellman
Synthetic protocols and circular dichroism (CD) spectra are reported for a series of oligomers of (R,R)-trans-2-aminocyclopentanecarboxylic acid (trans-ACPC). The two longest oligomers, a hexamer and an octamer, have also been examined crystallographically. Both crystal structures show that the â-peptide backbone adopts a regular helix that is defined by a series of interwoven 12-membered ring hydrogen bonds (“12-helix”). Each hydrogen bond links a carbonyl oxygen to an amide proton three residues toward the C-terminus. CD data suggest that the conformational preference of trans-ACPC oligomers in methanol is strongly length-dependent, which implies that 12-helix formation is a cooperative process, as seen for the R-helix formed by conventional peptides. Previous work has established that oligomers and polymers of â-amino acids can adopt helical conformations, but the 12-helix is an unprecedented â-peptide secondary structure.
Circular dichroism, Secondary structure, Stereochemistry, Biochemistry