title: The roles of side chain and backbone in protein structure probed with glycine- and sarcosine-rich synthetic leucine zipper peptides.
abstract: The protein folding problem has long been a formidable challenge. Here we present a synthetic natural motif approach that exploits small preexisting structural models for the dissection of forces important in protein folding. An example for this approach is shown in the modification of a 31-residue leucine zipper peptide with the helix-breaking amino acid glycine and the hydrogen bond-breaking imino acid sarcosine. Circular dichroism and NMR experiments have shown that the glycine-modified leucine zipper peptide adopts a stable helical conformation similar to the native conformation while the sarcosine-modified leucine zipper peptide adopts a random coil conformation. These results provide valuable insight into the current controversy over the relative importance of long-range side chain-side chain interactions versus local backbone interactions in protein structure and suggest that the natural motif strategy may represent a useful model to study protein folding.
authors.affiliation: Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Butcher
authors.forename: Z
authors.initials: Z
authors.lastname: Luo
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D005998:Glycine / Q000737:chemistry; D016350:Leucine Zippers; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012521:Sarcosine / Q000737:chemistry
chemical_list: D010455:Peptides; D011506:Proteins; D005998:Glycine; D012521:Sarcosine