title: Tryptophan rich peptides: influence of indole rings on backbone conformation.
abstract: Synthetic peptides with defined secondary structure scaffolds, namely hairpins and helices, containing tryptophan residues, have been investigated in this study to probe the influence of a large number of aromatic amino acids on backbone conformations. Solution NMR investigations of Boc-W-L-W-(D)P-G-W-L-W-OMe (peptide 1), designed to form a well-folded hairpin, clearly indicates the influence of flanking aromatic residues at the (D)Pro-Gly region on both turn nucleation and strand propagation. Indole-pyrrolidine interactions in this peptide lead to the formation of the less-frequent type I' turn at the (D)Pro-Gly segment and frayed strand regions, with the strand residues adopting local helical conformations. An analog of peptide 1 with an Aib-Gly turn-nucleated hairpin (Boc-W-L-W-U-G-W-L-W-OMe (peptide 2)) shows a preference for helical structures in solution, in both chloroform and methanol. Peptides with either one (Boc-W-L-W-U-W-L-W-OMe (peptide 3)) or two (Boc-U-W-L-W-U-W-L-W-OMe (peptide 4)) helix-nucleating Aib residues give rise to the well-folded helical conformations in the chloroform solution. The results are indicative of a preference for helical folding in peptides containing a large number of Trp residues. Investigation of a tetrapeptide analog of peptide 2, Boc-W-U-G-W-OMe (peptide 5), in solution and in the crystal state (by X-ray diffraction), also indicates a preference for a helical fold. Additionally, peptide 5 is stabilized in crystals by both aromatic interactions and an array of weak interactions. Examination of Trp-rich sequences in protein structures, however, reveals no secondary structure preference, suggesting that other stabilizing interactions in a well-folded protein may offset the influence of indole rings on backbone conformations.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahalakshmi
authors.forename: Anindita
authors.initials: A
authors.lastname: Sengupta
authors.forename: Srinivasarao
authors.initials: S
authors.lastname: Raghothama
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Shamala
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Balaram
mesh_terms: D000595:Amino Acid Sequence; D001704:Biopolymers / Q000737:chemistry; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions; D055672:Static Electricity; D014364:Tryptophan / Q000737:chemistry
chemical_list: D001704:Biopolymers; D007211:Indoles; D009842:Oligopeptides; D012996:Solutions; D014364:Tryptophan