Peptide hairpins with strand segments containing α- and β-amino acid residues: Cross-strand aromatic interactions of facing Phe residues

The incporation of β-amino acid residues into the strand segments of designed β-hairpin leads to the formation of polar sheets, since in the case of β-peptide strands, all adjacent carbonyl groups point in one direction and the amide groups orient in the opposite direction. The conformational analysis of two designed peptide hairpins composed of α/β-hybrid segments are described: Boc-βLeu-βPhe-Val-D-Pro-Gly-βLeu-βPhe-Val-OMe (1) and Boc-βLeu-Phe-βVal-D-Pro-Gly-βLeu-Phe-βVal-OMe (2). A 500-MHz 1H-NMR (nuclear magnetic resonance) analysis in methanol supports a significant population of hairpin conformations in both peptides. Diagnostic nuclear Overhauser effects (NOEs) are observed in both cases. X-ray diffraction studies on single crystals of peptide 1 reveal a β-hairpin conformation in both the molecules, which constitute the crystallographic asymmetric unit. Three cross-strand hydrogen bonds and a nucleating type II′ β-turn at the D-Pro-Gly segment are observed in the two independent molecules. In peptide 1, the Phe residues at positions 2 and 7 occur at the nonhydrogen-bonding position, with the benzyl side chains pointing on opposite faces of the β-sheet. The observed aromatic centroid-to-centroid distances are 8.92 Å (molecule A) and 8.94 Å (molecule B). In peptide 2, the aromatic rings must occupy facing positions in antiparallel strands, in the NMR-derived structure. Peptide 1 yields a normal hairpin-like CD spectrum in methanol with a minimum at 224 nm. The CD spectrum of peptide 2 reveals a negative band at 234 nm and a positive band at 221 nm, suggestive of an exciton split doublet. Modeling of the facing Phe side chains at the hydrogen-bonding position of a canonical β-hairpin suggests that interring separation is 4.78 Å for the gauche+gauche- (g+g-) rotamer. A previously reported peptide β-hairpin composed of only α-amino acids, Boc-Leu-Phe-Val-D-Pro-Gly-Leu-Phe-Val-OMe also exhibited an anomalous far-UV (ultraviolet) CD (circular dichroism) spectrum, which was interpreted in terms of interactions between facing aromatic chromophores, Phe 2 and Phe

Coulomb dissociation of N 20,21

Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N20,21 are reported. Relativistic N20,21 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the N19(n,γ)N20 and N20(n,γ)N21 excitation functions and thermonuclear reaction rates have been determined. The N19(n,γ)N20 rate is up to a factor of 5 higher at

Non-protein amino acids in peptide design

An overview of the use of non-protein amino acids in the design of conformationally well-defined peptides, based on work from the author’s laboratory, is discussed. The crystal structures of several designed oligopeptides illustrate the use alpha-aminoisobutyric acid (Aib) in the construction of helices, D-amino acids in the design of helix termination segments and DPro–Xxx segments for nucleating of beta-hairpin structures. beta- and gamma-amino acid residues have been used to expand the range of designed polypeptide structures

α,β\alpha,\betahybrid peptides:a polypeptide helix with a central segment containing two consecutive β\beta-amino acid residues

Conformational studies on the synthetic 11-aa peptide t-butoxycarbonyl (Boc)-Val-Ala-Phe-$\alpha$-aminoisobutyric acid (Aib)-(R)-$\beta^3$- homovaline ($\beta$Val)-(S)-$\beta^3$-homophenylalanine ($\beta$Phe)-Aib-Val-Ala- Phe-Aib-methyl ester (OMe) (peptide 1; $\beta$Val and $\beta$Phe are $\beta$amino acids generated by homologation of the corresponding L-residues) establish that insertion of two consecutive $\beta$ residues into a polypeptide helix can be accomplished without significant structural distortion. Crystal-structure analysis reveals a continuous helical conformation encompassing the segment of residues 2–10 of peptide 1. At the site of insertion of the $\beta\beta$ segment, helical hydrogen-bonded rings are expanded. A C_1_5 hydrogen bond for the $\alpha\beta\beta$segment and two C_1_4 hydrogen bonds for the $\alpha\alpha\beta$or $\beta\alpha\alpha$ segments have been characterized. The following conformational angles were determined from the crystal structure for the $\beta$ residues: $\beta$ Val-5 ($\phi = -126 ^o$,$\theta = 76 ^o$ , and $\psi = -124$) and $\beta$Phe-6 ($\phi = - 88^o,$ $\theta = 80^o,$ and $\psi = - 118$). The N terminus of the peptide is partially unfolded in crystals. The 500-MHz $^1H-NMR$ studies establish a continuous helix over the entire length of the peptide in $CDCl_3$ solution, as evidenced by diagnostic nuclear Overhauser effects. The presence of seven intramolecular hydrogen bonds is also established by using solvent dependence of NH chemical shifts

Aggregation modes in sheets formed by protected β-amino acids and β-peptides

The crystal structures of four protected β-amino acid residues, Boc-(S)-β3-HAla-NHMe (1); Boc-(R)-β3-HVal-NHMe (2); Boc-(S)-β3-HPhe-NHMe (3); Boc-(S)-β3-HPro-OH (6) and two β-dipeptides, Boc-(R)-β3-HVal-(R)-β3-HVal-OMe (4); Boc-(R)-β3-HVal-(S)-β3-HVal-OMe (5) have been determined. Gauche conformations about the Cβ-Cα bonds (θ~ ±60°) are observed for the β3-HPhe residues in 3 and all four β3-HVal residues in the dipeptides 4 and 5. Trans conformations (θ~180°) are observed for β3-HAla residues in both independent molecules in 1 and for the β3-HVal and β3-HPro residues in 2 and 6, respectively. In the cases of compounds 1-5, molecules associate in the crystals via intermolecular backbone hydrogen bonds leading to the formation of sheets. The polar strands formed by β3-residues aggregate in both parallel (1, 3, 5) and antiparallel (2, 4) fashion. Sheet formation accommodates both the trans and gauche conformations about the Cβ-Cα bonds

Aggregation modes in sheets formed by protected β {\beta} -aminoacids and β{\beta}-peptides

The crystal structures of four protected ${\beta}$-amino acid residues,Boc-(S)-${\beta}{^3}$-HAla-NHMe(1);Boc-(R)-${\beta}{^3}$-HVal-NHMe(2);Boc-(S)-${\beta}{^3}$-HPhe-NHMe(3);Boc-(S)-${\beta}{^3}$-HPro-OH(6) and two ${\beta}$-dipeptides,Boc-(R)-${\beta}{^3}$-HVal-(R)-${\beta}{^3}$-HVal-OMe(4);Boc-(R)-${\beta}{^3}$-HVal-(S)-${\beta}{^3}$ HVal-OMe(5) have been determined. Gauche conformations about the $C{^\beta}$ –$C{^\alpha}$ bonds$(\theta{\sim}{\pm}60){^o}$ are observed for the ${\beta}{^3}$-HPhe residues in 3 and all four ${\beta}{^3}$-HVal residues in the dipeptides 4 and 5. Trans conformations $(\theta{\sim}180{^0})$ are observed for ${\beta}{^3}$-HAla residues in both independent molecules in 1 and for the ${\beta}{^3}$-HVal and ${\beta}{^3}$-HPro residues in 2 and 6, respectively. In the cases of compounds 1–5, molecules associate in the crystals via intermolecular backbone hydrogen bonds leading to the formation of sheets. The polar strands formed by ${\beta}{^3}$-residues aggregate in both parallel(1, 3, 5) and antiparallel (2, 4) fashion. Sheet formation accommodates both the trans and gauche conformations about the $C{^\beta}$-$C{^\alpha}$ bonds

Beta-Hairpins Generated from Hybrid Peptide Sequences Containing both Alpha- and Beta-Amino Acids

The incorporation of the -amino acid residues into specific positions in the strands and -turn segments of peptide hairpins is being systematically explored. The presence of an additional torsion variable about the C()C() bond () enhances the conformational repertoire in -residues. The conformational analysis of three designed peptide hairpins composed of /-hybrid segments is described: Boc-Leu-Val-Val-DPro-Phe- Leu-Val-Val-OMe (1), Boc-Leu-Val-Val-DPro-Gly-Leu-Val-Val-OMe (2), and Boc-Leu-Val-Phe-Val-DPro- Gly-Leu-Phe-Val-Val-OMe (3). 500-MHz 1H-NMR Analysis supports a preponderance of -hairpin conformation in solution for all three peptides, with critical cross-strand NOEs providing evidence for the proposed structures. The crystal structure of peptide 2 reveals a -hairpin conformation with two -residues occupying facing, non-H-bonded positions in antiparallel -strands. Notably, Val(3 ) adopts a gauche conformation about the C()C() bond (65) without disturbing cross-strand H-bonding. The crystal structure of 2, together with previously published crystal structures of peptides 3 and Boc-Phe-Phe-DPro-Gly- Phe-Phe-OMe, provide an opportunity to visualize the packing of peptide sheets with local −polar segments× formed as a consequence of reversal peptide-bond orientation. The available structural evidence for hairpins suggests that -residues can be accommodated into nucleating turn segments and into both the H-bonding and non-H-bonding positions on the strands

Hybrid peptide hairpins containing alpha- and omega-amino acids: Conformational analysis of decapeptides with unsubstituted beta-, gamma-, and delta-residues at positions 3 and 8

The effects of inserting unsubstituted omega-amino acids into the strand segments of model beta-hairpin peptides was investigated by using four synthetic decapeptides, Boc-Lcu-Val-Xxx-Val-D-Pro-Gly-Leu-Xxx-Val-Val- OMe: pepticle 1 (Xxx=Gly), pepticle 2 (Xxx=beta Gly=beta hGly=homoglycine, beta-glycine), pepticle 3 (Xxx=gamma Abu=gamma-aminobutyric acid), pepticle 4 (Xxx= delta Ava=delta-aminovaleric acid). H-1 NMR studies (500 MHz, methanol) reveal several critical cross-strand NOEs, providing evidence for P-hairpin conformations in peptides 2-4. In peptide 3, the NMR results support the formation of the nucleating turn, however, evidence for cross-strand registry is not detected. Single-crystal X-ray diffraction studies of peptide 3 reveal a beta-hairpin conformation for both molecules in the crystallographic asymmetric unit, stabilized by four cross-strand hydrogen bonds, with the gamma Abu residues accommodated within the strands. The D-Pro-Gly segment in both molecules (A,B) adopts a type II' beta-turn conformation. The circular dichroism spectrum for peptide 3 is characterized by a negative CD band at 229 rim, whereas for peptides 2 and 4, the negative band is centered at 225 nm, suggesting a correlation between the orientation of the amide units in the strand segments and the observed CD pattern

Peptide Hairpins with Strand Segments Containing \alpha - and \beta - Amino Acid Residues: Cross- Strand Aromatic Interactions of Facing Phe Residues

The incporation of \beta -amino acid residues into the strand segments of designed \beta -hairpin leads to the formation of polar sheets, since in the case of \beta -peptide strands, all adjacent carbonyl groups point in one direction and the amide groups orient in the opposite direction. The conformational analysis of two designed peptide hairpins composed of \alpha /\beta -hybrid segments are described: Boc-Leu-\beta Phe-Val-D-Leu-\beta -OMe (1) and Boc-\beta Leu-Phe-\beta Val-DPro-Gly-\beta Leu-Phe-\beta Val-OMe (2). A 500-MHz 1H-NMR (nuclear magnetic resonance) analysis in methanol supports a signi.cant population of hairpin conformations in both peptides. Diagnostic nuclear Overhauser effects (NOEs) are observed in both cases. X-ray diffraction studies on single crystals of peptide 1 reveal a \beta -hairpin conformation in both the molecules, which constitute the crystallographic asymmetric unit. Three cross-strand hydrogen bonds and a nucleating type II0 \beta -turn at the D-Pro-Gly segment are observed in the two independent molecules. In peptide 1, the \beta Phe residues at positions 2 and 7 occur at the nonhydrogen-bonding position, with the benzyl side chains pointing on opposite faces of the \beta -sheet. The observed aromatic centroid-to-centroid distances are 8.92A (molecule A) and 8.94A (molecule B). In peptide 2, the aromatic rings must occupy facing positions in antiparallel strands, in the NMR-derived structure