title: Salt-bridging effects on short amphiphilic helical structure and introducing sequence-based short beta-turn motifs.
abstract: Determining the minimal sequence necessary to induce protein folding is beneficial in understanding the role of protein-protein interactions in biological systems, as their three-dimensional structures often dictate their activity. Proteins are generally comprised of discrete secondary structures, from α-helices to β-turns and larger β-sheets, each of which is influenced by its primary structure. Manipulating the sequence of short, moderately helical peptides can help elucidate the influences on folding. We created two new scaffolds based on a modestly helical eight-residue peptide, PT3, we previously published. Using circular dichroism (CD) spectroscopy and changing the possible salt-bridging residues to new combinations of Lys, Arg, Glu, and Asp, we found that our most helical improvements came from the Arg-Glu combination, whereas the Lys-Asp was not significantly different from the Lys-Glu of the parent scaffold, PT3. The marked 310-helical contributions in PT3 were lessened in the Arg-Glu-containing peptide with the beginning of cooperative unfolding seen through a thermal denaturation. However, a unique and unexpected signature was seen for the denaturation of the Lys-Asp peptide which could help elucidate the stages of folding between the 310and α-helix. In addition, we developed a short six-residue peptide with β-turn/sheet CD signature, again to help study minimal sequences needed for folding. Overall, the results indicate that improvements made to short peptide scaffolds by fine-tuning the salt-bridging residues can enhance scaffold structure. Likewise, with the results from the new, short β-turn motif, these can help impact future peptidomimetic designs in creating biologically useful, short, structured β-sheet-forming peptides.
authors.affiliation: a Department of Chemistry , The College of New Jersey , 2000 Pennington Road, Ewing , NJ , USA.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Guarracino
authors.affiliation: a Department of Chemistry , The College of New Jersey , 2000 Pennington Road, Ewing , NJ , USA.
authors.forename: Kayla
authors.initials: K
authors.lastname: Gentile
authors.affiliation: a Department of Chemistry , The College of New Jersey , 2000 Pennington Road, Ewing , NJ , USA.
authors.forename: Alec
authors.initials: A
authors.lastname: Grossman
authors.affiliation: a Department of Chemistry , The College of New Jersey , 2000 Pennington Road, Ewing , NJ , USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Li
authors.affiliation: a Department of Chemistry , The College of New Jersey , 2000 Pennington Road, Ewing , NJ , USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Refai
authors.affiliation: a Department of Chemistry , The College of New Jersey , 2000 Pennington Road, Ewing , NJ , USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Mohnot
authors.affiliation: a Department of Chemistry , The College of New Jersey , 2000 Pennington Road, Ewing , NJ , USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: King
mesh_terms: D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D011489:Protein Denaturation; D017510:Protein Folding; D060066:Protein Interaction Maps; D013057:Spectrum Analysis
chemical_list: D000596:Amino Acids
keywords: beta-turns; circular dichroism; folding; helices; peptides; salt-bridging