Antigenic mimicry of natural L-peptides with retro-inverso-peptidomimetics.

Guichard, Gilles; Benkirane, Nadia; Zeder‐Lutz, Gabrielle; Regenmortel, M.H.V. Van; Briand, Jean‐Paul; Muller, Sylviane

doi:10.1073/pnas.91.21.9765

Cited by 150 publications

(105 citation statements)

References 30 publications

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“…We previously observed the recovery of some peptides from the J404 phage display library that fit the consensus if listed in reverse order (40,46,47), and the cross-reactivity of antibodies with retropeptides has been specifically addressed (48). We also observed that the reverse sequence of a bioactive peptide shows significantly greater effects than a peptide bearing a randomly chosen sequence (49).…”

Section: -K-n -P/r -(X)-v-r-g-qmentioning

confidence: 95%

Phage Display Epitope Mapping of Human Neutrophil Flavocytochromeb 558

Burritt

DeLeo²,

McDonald

et al. 2001

Journal of Biological Chemistry

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. is formed. In this functional capacity, Cyt b has been established as an essential component of the respiratory burst oxidase, although little published experimental data describe its topology in the membrane. Determination of structural and functional aspects of epitopes bound by specific antibodies can provide information about the protein against which the antibody is directed (11). Antipeptide and antisubunit polyclonal antibodies against regions of Cyt b have been used to locate the corresponding epitopes (12, 13) and information derived from identification of epitope mimetics has led to the description of anti-Cyt b "antibody imprints" (14). We continue to elucidate the structure of Cyt b domains recognized by monoclonal antibodies to better define its transmembrane topology and gain insight into its functional organization.Reported epitope mapping data for monoclonal antibodies (mAbs) specific for Cyt b indicate that they bind cytosolic aspects of the protein (15-19). However, it has been reported that mAb 7D5 (19) binds an extracellular Cyt b epitope on intact neutrophils derived from normal but not CGD patients that lack Cyt b (20). Thus, 7D5 has proven useful in the determination of Cyt b up-regulation as an indicator of neutrophil activation and granule exocytosis (21) and for the identification of individuals deficient in Cyt b (20,22,23). However, neither the subunit location nor chemical nature of the 7D5 epitope has been elucidated.In our current studies, we have used phage display and immunological analyses to identify the 7D5 epitope on Cyt b. Although we confirmed the inability of 7D5 to recognize Cyt b on immunoblots, we found that 7D5 immunoprecipitated detergent-solubilized Cyt b heterodimer containing its fully processed 91kDa form of gp91 phox and its 65-kDa precursor. Additionally, it precipitated the deglycosylated gp91 phox core protein, 2 suggesting that neither the mature nor high man-* This work was performed during the tenure of the following American Heart Association awards: postdoctoral fellowships 9704584S

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Section: -K-n -P/r -(X)-v-r-g-qmentioning

confidence: 95%

Phage Display Epitope Mapping of Human Neutrophil Flavocytochromeb 558

Burritt

DeLeo²,

McDonald

et al. 2001

Journal of Biological Chemistry

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“…Control experiments were carried out with the L-and retro-inverso peptides of sequence IRGERA. These peptides, as well as the anti-IRGERA monoclonal antibody 4x11, were described previously (8,9).…”

Section: Gsgvrgdfgslaprvarqlmentioning

confidence: 99%

“…The enhanced immunogenic reactivities of retro-inverso analogues may result from their higher resistance to proteolysis in biological fluids (7). However, this property does not explain why in immunochemical assays, retro-inverso peptides are often better recognized than the parent peptide by anti-virus, anti-protein, or anti-peptide antibodies with equilibrium affinity constants which can be increased by 10 -100 in some instances (7)(8)(9).…”

mentioning

confidence: 99%

Solution Structure of a Retro-inverso Peptide Analogue Mimicking the Foot-and-Mouth Disease Virus Major Antigenic Site

Petit¹,

Benkirane²,

Guichard³

et al. 1999

Journal of Biological Chemistry

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The antigenic activity of a 19-mer peptide corresponding to the major antigenic region of foot-and-mouth disease virus and its retro-enantiomeric analogue was found to be completely abolished when they were tested in a biosensor system in trifluoroethanol. This suggests that the folding pattern, which is ␣-helix in trifluoroethanol (confirmed by CD measurement), does not correspond to the biologically relevant conformation(s) recognized by antibodies. The NMR structures of both peptides were thus determined in aqueous solution. These studies showed that the two peptides exhibit similar folding features, particularly in their C termini. This may explain in part the cross-reactive properties of the two peptides in aqueous solution. However, the retro-inverso analogue appears to be more rigid than the parent peptide and contains five atypical ␤-turns. This feature may explain why retro-inverso foot-andmouth disease virus peptides are often better recognized than the parent peptide by anti-virion antibodies.The major immunogenic site of foot-and-mouth disease virus (FMDV), 1 which is contained in the so-called G-H loop comprising amino acid residues 135-158 of capsid protein VP1 (viral capsid protein 1), is located in a disordered region on the surface of the particle (1). A single inoculum of a peptide corresponding to this region usually elicits levels of neutralizing antibodies that protect guinea pigs against a severe challenge with the cognate virus (2). In some instances, however, although the total reactivity of antibodies evaluated in immunochemical tests such as enzyme-linked immunosorbent assay is high, the level of neutralizing antibodies is low. This important problem has generated numerous studies aimed at enhancing the immunogenicity of this peptide with the hope of developing a peptide construct that could be used successfully as a synthetic vaccine (3). Recently, we have shown that antisera raised in rabbits against peptides corresponding to the sequence 141-159 of two variants of serotype A cross-reacted strongly with the corresponding retro-inverso analogue peptides. Most importantly, the retro-inverso analogues, also called retro all-D or retro-enantio peptides (4, 5), induced greater and longer-lasting antibody titers than did the respective parent peptides (6). Moreover, we showed with the FP variant analogue (which contains Phe and Pro residues at positions 148 and 153, respectively) that a single inoculation of the retro-inverso peptide elicited high levels of neutralizing antibodies that persisted longer than those induced against the corresponding L-peptide and protected guinea pigs challenged with the cognate virus (7). The enhanced immunogenic reactivities of retro-inverso analogues may result from their higher resistance to proteolysis in biological fluids (7). However, this property does not explain why in immunochemical assays, retro-inverso peptides are often better recognized than the parent peptide by anti-virus, anti-protein, or anti-peptide antibodies with equilibrium affinity cons...

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“…Shai and co-workers have reported that D peptides corresponding to transmembrane helices of several integral membrane proteins can pair with the natural L-peptide helix within a lipid bilayer (9)(10)(11). The retroinverso design strategy has been widely used in pursuit of biologically active D peptides; however, results from this approach have been mixed (12)(13)(14)(15). Computationally designed D peptides that inhibit formation of amyloid fibrils by a Tau-derived L polypeptide have been reported (16).…”

mentioning

confidence: 99%

High-resolution structures of a heterochiral coiled coil

Mortenson

Steinkruger

Kreitler

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Interactions between polypeptide chains containing amino acid residues with opposite absolute configurations have long been a source of interest and speculation, but there is very little structural information for such heterochiral associations. The need to address this lacuna has grown in recent years because of increasing interest in the use of peptides generated from D amino acids (D peptides) as specific ligands for natural proteins, e.g., to inhibit deleterious proteinprotein interactions. Coiled-coil interactions, between or among α-helices, represent the most common tertiary and quaternary packing motif in proteins. Heterochiral coiled-coil interactions were predicted over 50 years ago by Crick, and limited experimental data obtained in solution suggest that such interactions can indeed occur. To address the dearth of atomic-level structural characterization of heterochiral helix pairings, we report two independent crystal structures that elucidate coiled-coil packing between L-and D-peptide helices. Both structures resulted from racemic crystallization of a peptide corresponding to the transmembrane segment of the influenza M2 protein. Networks of canonical knobs-into-holes side-chain packing interactions are observed at each helical interface. However, the underlying patterns for these heterochiral coiled coils seem to deviate from the heptad sequence repeat that is characteristic of most homochiral analogs, with an apparent preference for a hendecad repeat pattern.D peptides | transmembrane peptides | racemic crystallization | racemic detergent | coiled coil P olypeptides comprising D-amino acid residues have been sources of growing interest for biological applications, often for functions that depend on recognition by specific natural proteins (1-3). D peptides offer identical versatility in terms of conformation and side-chain functionality relative to conventional peptides (composed of L-amino acid residues), but D peptides are impervious to the action of proteolytic enzymes, which should improve pharmacokinetic properties in vivo relative to those of conventional peptides. The engineering of D peptides to display defined protein-binding preferences is hindered, however, by the dearth of experimental information available for such complexes. Structural principles that are well-known to govern interactions between two L-polypeptide chains are not directly extensible to pairings between peptides of opposite chirality. Favorable heterochiral interactions (between L-and D peptides) that are analogous to homochiral associations between L peptides were postulated decades ago on the basis of geometrical considerations (4, 5). In a 1953 analysis of structural parameters governing coiled-coil formation between right-handed α-helices formed from L peptides, for example, Crick suggested that analogous assemblies should be accessible to pairs of right-and left-handed helices (4). In the same year, Pauling and Corey postulated that heterochiral peptide mixtures could form "rippled" β-sheet assemblies with backbo...

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Antigenic mimicry of natural L-peptides with retro-inverso-peptidomimetics.

Cited by 150 publications

References 30 publications

Phage Display Epitope Mapping of Human Neutrophil Flavocytochromeb 558

Phage Display Epitope Mapping of Human Neutrophil Flavocytochromeb 558

Solution Structure of a Retro-inverso Peptide Analogue Mimicking the Foot-and-Mouth Disease Virus Major Antigenic Site

High-resolution structures of a heterochiral coiled coil

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