On the concept of linear modified retro-peptide structures

Goodman, Murray; Chorev, Michael

doi:10.1021/ar50133a001

Cited by 245 publications

(145 citation statements)

References 34 publications

Supporting

Mentioning

144

Contrasting

Order By: Relevance

“…The retroinverso analogue is obtained by replacing the normal L-amino acid residues by the corresponding D-amino acids and by reversing the direction of the peptide backbone. This results in maintenance of the side chain topochemistry-i.e., the original spatial orientation of all side chains is retained (23). In the case ofthe retro analogue, the backbone is reversed but the chirality of amino acids in the sequence is retained, resulting in a noncomplementary side chain topochemistry between this analogue and the parent L-peptide.…”

mentioning

confidence: 99%

“…However, in such linear peptides, the two pairs of topochemically related peptides do not share end group and charge complementarity. To solve this end-group problem, a gemdiaminoalkyl residue can be introduced at the amino terminus and a 2-substituted malonic acid can be introduced at the carboxyl terminus (23). However, monoacyl gem-diaminoalkyls are hydrolyzed, and one should expect the half-life of peptides incorporating such residues to be 10-50 hr at 250C (24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Guichard

Benkirane

Zeder‐Lutz

et al. 1994

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

152

100

View full text Add to dashboard Cite

Three analogues of the model peptide of sequence IRGERA corresponding to the COOH-terminal residues 130-135 of histone H3 were synthesized, and their antigenicity, immunogenicity, and resistance to trypsin were compared to those of the natural L-peptide. The three analogues correspond to the D-enantiomer, containing only D-residues, and two retro-peptides containing NH-CO bonds instead of natural peptide bonds. The chirality of each residue was maintained in the retro-peptide and inverted in the retroinverso-peptide. Antibodies to the four peptide analogues were produced by injecting BALB/c mice with peptides covalently coupled to small unilamellar liposomes containing monophosphoryl lipid A. Each of the four peptide analogues induced IgG antibodies of various subclasses. The IgG3 antibodies reacted similarly with the four analogues, whereas antibodies of the IgGl, IgG2a, and IgG2b isotypes showed strong conformational preferences for certain peptides. The retro-inversopeptide IRGERA mimicked the structure and antigenic activity of the natural L-peptide but not of the D-and retro-peptides, whereas the retro-peptide IRGERA mimicked the D-peptide but not the L-and retro-inverso-peptides. The equilibrium affnity constants (Ka) of three monoclonal antibodies generated against the L-and D-peptides with respect to the four peptide analogues were measured in a biosensor system. Large differences in Ka values were observed when each monoclonal antibody was tested with respect to the four peptides. The use of retro-inverso-peptides to replace natural L-peptides is likely to find many applications in immunodiagnosis and as potential synthetic vaccines.The development of neuropeptides, peptide hormones, peptide antibiotics, or peptide-based synthetic vaccines is strongly impaired by the high susceptibility of peptides to proteolysis, which limits, inter alia, parental and oral administration. For many years intense work has been focused on the synthesis of peptide analogues in the search for mimics with enhanced activity and biological half-lives. Examples of modifications introduced in peptides are the replacement of L-amino acid residues by D-amino acids or by unnatural residues (e.g., sarcosine and 3-alanine) and the modification of peptide bonds (1-3). These changes provide pseudopeptides or peptidomimetics with a higher metabolic stability, since most natural proteases cannot cleave D-amino acid residues and nonpeptide bonds. An important problem encountered with such peptide analogues is the conservation of their biological activity. Recently, the D-form of human immunodeficiency virus type 1 protease has been synthesized (4). As could be expected, the enantiomeric protein displayed reciprocal chiral specificity as the enzyme was unable to cleave the normal L-substrate but did hydrolyze its D-enantiomer. In contrast, Wen and Laursen (5) showed that both the L-and D-form of an a-helical antifreeze polypeptide bound equally well to the same achiral ice substrate, whereas Wade et al. (6) found that the L-and D-e...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Guichard

Benkirane

Zeder‐Lutz

et al. 1994

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

152

100

View full text Add to dashboard Cite

show abstract

“…25 Molecular dynamic simulation of the amino acid surrogate residues identified energy barriers between the helical and extended conformations that can be easily overcome by the formation of the two hydrogen bonds per residue in the parallel ␤-sheet aggregate observed in the crystal structure. Interestingly, there is a good correspondence between the characteristic theoretical conformational space attributed to both (AcNH) 2 …”

Section: Conformational Features Of the Amino Acid Surrogates Involvementioning

confidence: 73%

“…Jointly we explored the synthetic routes for the construction of retro-inverso (RI) peptide bonds in linear peptides, sorted their stereochemical and conformational properties, analyzed this structural transformation conceptually, monitored its development by others, and periodically summarized the state of the art in reviews and opinion articles. [2][3][4][5][6] During this adventure, we formulated new concepts, tested new hypotheses, and spent many hours in heated discussions in Murray's office, around the pool in La Jolla, over the phone, through the Internet, and at various meeting points around the globe. We shared the delight and satisfaction of seeing new insights and applications generated by others as the RI modification spread to laboratories around the world in many cases leading to fascinating findings.…”

Section: Introductionmentioning

confidence: 99%

The partial retro–inverso modification: A road traveled together

Chorev

2005

Biopolymers

Self Cite

View full text Add to dashboard Cite

“…It was expected that a ri-peptide analog corresponding to a given sequence should adopt a conformation similar to that of the corresponding L peptide (11). Therefore, we built the conformational models of ri analogs of VSVp and OVAp (called ri-VSVp and ri-OVAp).…”

Section: Ri Versions Of the T Cell Epitopes Vsvp And Ovap Exhibit Cmentioning

confidence: 99%

Mimicry of Native Peptide Antigens by the Corresponding Retro-Inverso Analogs Is Dependent on Their Intrinsic Structure and Interaction Propensities

Nair

Kaur

Singh

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Retro-inverso (ri) analogs of model T cell and B cell epitopes were predictively designed as mimics and then assayed for activity to understand the basis of functional ri-antigenic peptide mimicry. ri versions of two MHC class I binding peptide epitopes, one from a vesicular stomatitis virus glycoprotein (VSVp) and another from OVA (OVAp), exhibit structural as well as functional mimicry of their native counterparts. The two ri peptides exhibit conformational plasticity and they bind to MHC class I (H-2Kb) similar to their native counterparts both in silico and in vivo. In fact, ri-OVAp is also presented to an OVAp-specific T cell line in a mode similar to native OVAp. In contrast, the ri version of an immunodominant B cell peptide epitope from a hepatitis B virus protein, PS1, exhibits no structural or functional correlation with its native counterpart. PS1 and its ri analog do not exhibit similar conformational propensities. PS1 is less flexible relative to its ri version. These observed structure-function relationships of the ri-peptide epitopes are consistent with the differences in recognition properties between peptide-MHC vs peptide-Ab binding where, while the recognition of the epitope by MHC is pattern based, the exquisitely specific recognition of Ag by Ab arises from the high complementarity between the Ag and the binding site of the Ab. It is evident that the correlation of conformational and interaction propensities of native l-peptides and their ri counterparts depends both on their inherent structural properties and on their mode of recognition.

show abstract

On the concept of linear modified retro-peptide structures

Cited by 245 publications

References 34 publications

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

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

The partial retro–inverso modification: A road traveled together

Mimicry of Native Peptide Antigens by the Corresponding Retro-Inverso Analogs Is Dependent on Their Intrinsic Structure and Interaction Propensities

Contact Info

Product

Resources

About