University of Wisconsin - La Crosse, Chemistry, La Crosse, WI 54601
Protein function is governed by physical characteristics such as flexibility and structure. The formation of secondary and tertiary structures is accomplished through the interaction of atoms and accompanying weak forces, which ultimately control protein flexibility. One of the most important weak forces is the hydrogen bond, which is found to occur between backbone atoms in secondary structures such as helices, sheets and coils. The most common helix conformation is the alpha-helix, characterized by an (i -> i + 4) hydrogen bonding pattern. A less common helix structure, sometimes found in protein binding sites and possibly as an intermediate during alpha-helical formation, is the 310-helix (characterized by an (i -> i + 3) hydrogen bonding pattern). It has been found that peptides primarily composed of the amino acid Aib (alpha-aminoisobutyric acid) will readily fold into 310-helices, even in peptides as short as three residues. Aib amino acids are structurally similar to alanine except for a methyl group in place of a hydrogen at the alpha-carbon. The dialkylation at the alpha-carbon creates significant steric hindrance, which is responsible for the helical preference of Aib. We are interested in the role that steric hidrance plays in governing helical structure and flexibility. The peptide of interest in this study is an eight residue chain with alanine amino acids at positions three and six and Aib residues at the remaining positions (“AA36”). Since Aib is sterically hindered and will drive the formation of a 310-helix, the two alanine residues will create two less sterically hindered and presumably more flexible regions of the helix. In this project, the AA36 peptide is prepared using solution phase synthesis, and 1H NMR is used to study amide proton exchange with deuterons in the solvent to characterize helical flexibility. The analysis of this data and comparison to that for similar peptides will lend insight to the role of steric hinderance and hydrogen bond strength in helix flexibility.
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