Linear stereocooligopeptides with alternating D and L residues. 3. Nature and relative stability of monomeric and dimeric species of the D,L-alternating octapeptide Boc-(L-Val-D-Val)4-OMe in cyclohexane or chloroform solution

Lorenzi, Gian Paolo; Jaeckle, Hans; Tomasic, Lera; Rizzo, Vincenzo; Pedone, Carlo

doi:10.1021/ja00370a047

Cited by 42 publications

(15 citation statements)

References 8 publications

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“…[2] Yet, due to its hydrophobicity, small size (15 residues), and ready availability, including the ease with which it can be synthesized or modified, gramicidin A (gA) has proven most valuable as a model for understanding the structure and function of transmembrane ion channels. [2] Accordingly, a number of gA derivatives [2] and model b-helical peptides [7][8][9][10][11][12][13][14][15][16] have been prepared over the past three decades; because the motive of these studies was to understand and mimic the structure and function of gA, these peptides were all hydrophobic and were examined almost exclusively in nonpolar media. [17] Meanwhile, the b-helical conformations of gA have been shown to be unstable in polar solvents; [18] for example, although gA is b-helical in methanol or ethanol that contains high concentrations of the nonpolar solvents chloroform or benzene, [18,19] the peptide is unstructured in the polar solvent dimethyl sulfoxide (DMSO).…”

Section: Introductionmentioning

confidence: 99%

Engineering a β‐Helical d,l‐Peptide for Folding in Polar Media

Kulp

Clark

2009

Chemistry A European J

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Beta helices--helices formed by alternating D,L-peptides and stabilized by beta-sheet hydrogen bonding--are found naturally in only a handful of highly hydrophobic peptides. This paper explores the scope of beta-helical structure by presenting the first design and biophysical characterization of a hydrophilic D,L-peptide, 1, that forms a beta helix in methanol. The design of 1 is based on the beta-hairpin/beta helix--a new supersecondary that had been characterized previously only for hydrophobic peptides in nonpolar solvents. Incorporating polar residues in 1 provided solubility in methanol, in which the peptide adopts the expected beta-hairpin/beta-helical structure, as evidenced by CD, analytical ultracentrifugation (AUC), NMR spectroscopy, and NMR-based structure calculations. Upon titration with water (at constant peptide concentration), the structure in methanol (1 m) transitions cooperatively to an extended conformation (1 w) resembling a cyclic beta-hairpin; observation of an isodichroic point in the solvent-dependent CD spectra indicates that this transition is a two-state process. In contrast, neither 1 m nor 1 w show cooperative thermal melting; instead, their structures appear intact at temperatures as high as 65 degrees C; this observation suggests that steric constraint is dominant in stabilizing these structures. Finally, the (1)H NMR C alphaH spectroscopic resonances of 1 m are downfield-shifted with respect to random-coil values, a hitherto unreported property for beta helices that appears to be a general feature of these structures. These results show for the first time that an appropriately designed beta-helical peptide can fold stably in a polar solvent; furthermore, the structural and spectroscopic data reported should prove useful in the future design and characterization of water-soluble beta helices.

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Section: Introductionmentioning

confidence: 99%

Engineering a β‐Helical d,l‐Peptide for Folding in Polar Media

Kulp

Clark

2009

Chemistry A European J

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“…For these peptides, which according to the polymer nomenclature are to be considered syndiotactic polymers, the existence of single monomeric /356-or double-stranded dimeric p 6-helical structures was established by nmr techniques in chloroform solution. 226 On the other hand, in the crystalline state both peptides were found as antiparallel doublestranded p5 6-helices. In particular, in the structure of Boc-( L-Val-D-Val),-OMe (Figure 2 5 ) , two octapeptide chains, related by a crystallographic binary axis, wind up around each other, giving rise to a double-stranded left-handed antiparallel p5 6- Boc-( ~-Val-~-Val),-OMel, which is 3 1 A long with an average diameter of 4.8 A.…”

Section: Heterochiral Peptidesmentioning

confidence: 99%

“…Solution conformational studies carried out on regularly alternating L,D peptides indicate that homopeptides made with different residues can assume different types of p-helical structures, [220][221][222] constituted by a single-or double-helical strands, which in turn can run either parallel or antiparallel to each other. The various types of P-helices are characterized by different helical parameters, such as the number of residue per turn and the pitch.…”

Section: Heterochiral Peptidesmentioning

confidence: 99%

X‐ray crystallography of peptides: The contributions of the Italian laboratories

Benedetti

1996

Biopolymers

139

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The review article summarizes the most relevant solid state structural and conformational results obtained in the laboratories involved in Italy in the studies of synthetic and natural peptides by x‐ray diffraction analyses. Some of the topics will include research studies carried out in other European countries, whereas in other cases studies carried out in Italy will be included in other review articles included in this volume. The review deals with peptides containing symmetrically achiral and unsymmetrically chiral Cα,α‐dialkylated glycine residues, peptides containing β‐alanine residues, α,β‐dehydroamino acid residues, and aminosuccinyl residues, peptides containing the thioamide surrogate, heterochiral peptides and several bioactive peptides systems with the proposed relationships between function and structure. © 1996 John Wiley & Sons, Inc.

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“…The analysis of the amide proton chemical shift is particularly interesting since a ␦ HN value higher than 7 ppm indicates that the amide proton is involved in a H-bond. 3,32,33 From Table I it can be deduced that only the HN of residue 9 does not form a H-bond in the main conformation. For the second conformation, it can be inferred that residues 2, 4, and 9 are not involved in a H-bond (Table II).…”

Section: Nmr Datamentioning

confidence: 99%

Conformational and structural analysis of the equilibrium between single‐ and double‐strand β‐helix of a D,L‐alternating oligonorleucine

2003

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Alternating sequences of D and L residues in peptides are directly related to the formation of several kinds of regular helical conformations usually called beta-helices. The major feature of these structures is that they can be associated with the transmembrane ion-conducting channel activity in some natural antibacterial peptides. The study of alternating D,L synthetic peptides is critical to understand how factors such as surrounding media, main chain length, type of side chain and terminal groups, among others, can determine the adoption of a specific kind of beta-helix. Early studies pointed out that the peptides Boc-(D-NLeu-L-NLeu)(6)-D-MeNLe-L-Nl-D-Nl-L-Nl-OMe (Boc: tert-butyloxycarbonyl) and Boc-L-Nle-(D-Nle-L-Nle)(5)-D-MeNle-L-Nle-D-Nle-L-Nle-OMe adopt in chloroform a unique detectable conformation single beta(4.4)- and double beta(5.6) upward arrow downward arrow -helix, respectively. The influence of terminal groups on the final stable conformation of N-formylated peptides has been studied in this work. The initial basic NMR data analysis of a synthetic alternating D,L-oligopeptide with ten norleucines, N-methylated on the residue 7 and having HCO- and -OMe as terminal groups clearly indicates the coexistence of two different conformations in equilibrium. NMR data and molecular dynamics calculations point to a dimeric antiparallel beta-helix structure beta(5.6) upward arrow downward arrow for the main conformation. On the other hand, NMR data suggest a single beta-helix structure beta(4.4) for the second conformation. Finally, a thermodynamic analysis of the equilibrium between both conformations has been carried out by one-dimensional NMR measurements at ten different temperatures. The temperature at which 50% of dimer conformation is dissociated is 319 K. In addition, the dimer-monomer equilibrium curve obtained shows a DeltaG>0 for the whole range of studied temperatures, and its behavior can be considered similar to the thermodynamic denaturation protein processes.

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Linear stereocooligopeptides with alternating D and L residues. 3. Nature and relative stability of monomeric and dimeric species of the D,L-alternating octapeptide Boc-(L-Val-D-Val)4-OMe in cyclohexane or chloroform solution

Cited by 42 publications

References 8 publications

Engineering a β‐Helical d,l‐Peptide for Folding in Polar Media

Engineering a β‐Helical d,l‐Peptide for Folding in Polar Media

X‐ray crystallography of peptides: The contributions of the Italian laboratories

Conformational and structural analysis of the equilibrium between single‐ and double‐strand β‐helix of a D,L‐alternating oligonorleucine

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