Conformation and Interaction of a <scp>d,l</scp>‐Alternating Peptide with a Bilayer Membrane: X‐ray Reflectivity, CD, and FTIR Spectroscopy

Küsel, Andrea; Khattari, Z. Y.; Schneggenburger, Philipp E.; Banerjee, Arnab; Salditt, Tim; Diederichsen, Ulf

doi:10.1002/cphc.200700477

Cited by 12 publications

(36 citation statements)

References 54 publications

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“…Considering the peptide structure as discussed earlier for oligomer 7 on the basis of CD and FTIR studies and comparing them to the extensively studied d,l-alternating configurated gramicidin A, two predominant structures are conceivable for these peptides. [16] Although the occurrence of the b -helix with a 3.3 pitch would feature a length of approximately 21 . [46][47][48][49][50] Considering these facts in addition to the CD results and previous studies, the distance indicated in the electron density difference curves by the major peaks that are located right beneath the lipid head-groups additionally suggest the existence of a membrane-spanning b 5.6 -helix.…”

Section: -Helices and X-ray Reflectivitymentioning

confidence: 99%

“…[16] The motif derived from gramicidin A is characterized by a membrane-spanning b 5.6 -helical dimer of antiparallel oriented and d,l-alternating configurated peptides. The tubular structures are supposed to anchor at the polar-hydrophobic head-group interface with their C-terminal tryptophane moieties spanning the hydrophobic membrane core without complete penetration of the lipid head-group region ( Figure 4).…”

Section: Transmembrane Peptide Design and Solid-phase Peptide Synthesismentioning

confidence: 99%

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A Novel Heavy‐Atom Label for Side‐Specific Peptide Iodination: Synthesis, Membrane Incorporation and X‐ray Reflectivity

et al. 2009

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Structural parameters, such as conformation, orientation and penetration depth of membrane-bound peptides and proteins that may function as channels, pores or biocatalysts, are of persistent interest and have to be probed in the native fluid state of a membrane. X-ray scattering in combination with heavy-atom labeling is a powerful and highly appropriate method to reveal the position of a certain amino acid residue within a lipid bilayer with respect to the membrane normal axis up to a resolution of several Angstrøm. Herein, we report the synthesis of a new iodine-labeled amino acid building block. This building block is intended for peptide incorporation to provide high intensities for electron density difference analysis of X-ray reflectivity data and improve the labeling potential for the lipid bilayer head-group and water region. The novel building block as well as the commercially available non-iodinated analogue, required for X-ray scattering, was implemented in a transmembrane peptide motif via manual solid-phase peptide synthesis (SPPS) following the fluorenylmethyloxycarbonyl (Fmoc)-strategy. The derived peptides were reconstituted in lipid vesicles as well as in highly aligned multilamellar lipid stacks and investigated via circular dichroism (CD) and X-ray reflectivity. Thereby, it has been revealed that the bulky iodine probe neither causes conformational change of the peptide structure nor lamellar disordering of the membrane complexes.

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Section: -Helices and X-ray Reflectivitymentioning

confidence: 99%

Section: Transmembrane Peptide Design and Solid-phase Peptide Synthesismentioning

confidence: 99%

A Novel Heavy‐Atom Label for Side‐Specific Peptide Iodination: Synthesis, Membrane Incorporation and X‐ray Reflectivity

et al. 2009

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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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“…FTIR spectra of the same peptide in water revealed that the β-sheet structure dominated at higher concentrations (76). The interaction of the polymer chain with conjugated peptide can be studied by X-ray reflectivity as well as CD and FTIR (77,78). Site-specific iodine labeling can be used to determine topology of the peptide within the self-assembled NPs by pinpointing the position of iodine label within NPs (77).…”

Section: Characterization Of Peptidomimetic Npsmentioning

confidence: 99%

Targeted Delivery with Peptidomimetic Conjugated Self-Assembled Nanoparticles

Jabbari

2008

Pharm Res

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Peptides produce specific nanostructures, making them useful for targeting in biological systems but they have low bioavailability, potential immunogenicity and poor metabolic stability. Peptidomimetic self-assembled NPs can possess biological recognition motifs as well as providing desired engineering properties. Inorganic NPs, coated with self-assembled macromers for stability and anti-fouling, and conjugated with target-specific ligands, are advancing imaging from the anatomy-based level to the molecular level. Ligand conjugated NPs are attractive for cell-selective tumor drug delivery, since this process has high transport capacity as well as ligand dependent cell specificity. Peptidomimetic NPs can provide stronger interaction with surface receptors on tumor cells, resulting in higher uptake and reduced drug resistance. Self-assembled NPs conjugated with peptidomimetic antigens are ideal for sustained presentation of vaccine antigens to dendritic cells and subsequent activation of T cell mediated adaptive immune response. Self-assembled NPs are a viable alternative to encapsulation for sustained delivery of proteins in tissue engineering. Cell penetrating peptides conjugated to NPs are used as intracellular delivery vectors for gene expression and as transfection agents for plasmid delivery. In this work, synthesis, characterization, properties, immunogenicity, and medical applications of peptidomimetic NPs in imaging, tumor delivery, vaccination, tissue engineering, and intracellular delivery are reviewed.

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Conformation and Interaction of a d,l‐Alternating Peptide with a Bilayer Membrane: X‐ray Reflectivity, CD, and FTIR Spectroscopy

Cited by 12 publications

References 54 publications

A Novel Heavy‐Atom Label for Side‐Specific Peptide Iodination: Synthesis, Membrane Incorporation and X‐ray Reflectivity

A Novel Heavy‐Atom Label for Side‐Specific Peptide Iodination: Synthesis, Membrane Incorporation and X‐ray Reflectivity

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

Targeted Delivery with Peptidomimetic Conjugated Self-Assembled Nanoparticles

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