Making sense from antisense: A review of experimental data and developing ideas on sense–antisense peptide recognition

Tropsha, Alexander; Kizer, John S.; Chaiken, Irwin M.

doi:10.1002/jmr.300050202

Cited by 53 publications

(35 citation statements)

References 76 publications

(80 reference statements)

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“…5,6 Since that time, many investigators have used this concept to identify proteins that interact, such as ligands with receptors, antigens with antibodies, and antibodies with antibodies. [7][8][9][10][11][12] It was later shown that antibodies against a sense protein and antibodies against the complement of that sense protein form an idiotypic pair through complementarity of their variable regions. 13 Idiotypic antibody pairs have been implicated in a number of autoimmune diseases, including myasthenia gravis, 14 Grave's disease, 15 and primary biliary cirrhosis.…”

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confidence: 99%

Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis

Bautz¹,

Preston²,

Lionaki³

et al. 2008

Journal of the American Society of Nephrology

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Patients with inflammatory vascular disease caused by anti-neutrophil cytoplasmic autoantibodies (ANCA) can harbor antibodies not only to the autoantigen proteinase 3 (PR3) but also to complementary PR3 (cPR3 ), a recombinant protein translated from the antisense strand of PR3 cDNA. The purpose of this study was to identify potential endogenous targets of anti-cPR3 antibodies. Patients' plasmapheresis material was tested for the presence of antigens reactive with affinity-purified rabbit and chicken anti-cPR3105-201 polyclonal antibodies. Antigen-containing fractions were tested with patients' anti-cPR3105-201 affinity-purified IgG, and putative protein targets were sequenced by mass spectrometry. Unexpectedly, plasminogen was identified as a target of anti-cPR3 . Reactivity of affinitypurified antibodies from two patients was lost when plasminogen was converted to plasmin, indicating restricted specificity. Antiplasminogen antibodies from five patients bound plasminogen at a surfaceexposed loop structure within the protease domain. This loop contains an amino acid motif that is also found in a portion of recombinant cPR3 ; site-directed mutagenesis of this sequence decreased antibody reactivity by 30%. Functionally, antiplasminogen antibodies delayed the conversion of plasminogen to plasmin and increased the dissolution time of fibrin clots. Serologically, antiplasminogen antibody levels were higher in PR3-ANCA patients (n ϭ 72) than healthy control subjects (n ϭ 63), myeloperoxidase-ANCA patients (n ϭ 34), and patients with idiopathic thrombosis (n ϭ 57; P ϭ 0.001). Of the patients with PR3-ANCA, nine had documented deep venous thrombosis events, five of whom were positive for antiplasminogen antibodies. In summary, capitalizing on interactions with complementary proteins, specifically complementary PR3, this study identified plasminogen as a previously undescribed autoantigen in PR3-ANCA vasculitis.

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confidence: 99%

Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis

Bautz¹,

Preston²,

Lionaki³

et al. 2008

Journal of the American Society of Nephrology

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“…Reported binding constants vary from nanomolar values to no measurable binding by different research group, technique used, and the particular antisense peptide being studied. 14,25,26 These experiments also negate any functional antisensebinding contractile-inhibition effect of Ang II antipeptides generated in the parallel reading frame. Although we were unable to complete a full activity curve for Root-Bernstein peptide (this procedure would have required approximately a gram of peptide to reach the high concentrations necessary), the data available suggest that the previously reported K d of Ϸ5ϫ10 Ϫ6 mol/L (Reference 13) is within the right range.…”

Section: Discussionmentioning

confidence: 66%

“…14,25,26 Calculated binding constants often assume direct binding of the antipeptide to its peptide in the absence of physicochemical evidence or despite direct evidence to the contrary. [43][44][45][46][47][48] In some cases, 45,49 the Root-Bernstein approach yields active antisense peptides when the Mekler-Biro-Blalock approach does not.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Two fundamentally different approaches to antisense peptide design have been used to generate both Ang II antipeptides and antisense peptides against other peptide targets. One, first suggested theoretically by Mekler,16 was reinvented later by Biro (reviewed in References 14,25,and 26). Among the unresolved issues of the field are whether these two approaches are interchangeable and whether the resulting peptides actually represent "complements" or antipeptides that bind directly to their target peptides.…”

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confidence: 99%

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Augmentation of Aortic Ring Contractions by Angiotensin II Antisense Peptide

1998

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Abstract-Previous biochemical experiments have revealed two antisense peptide antagonists to human angiotensin II (Ang II), one encoded in the cDNA in the antiparallel reading, the other in the parallel reading. Neither peptide's ability to produce physiological antagonism has been demonstrated previously. Both peptides were tested for their ability to antagonize Ang II-induced contractions on rabbit aorta smooth muscle. Neither peptide had any direct contractile activity. The antiparallel Ang II peptide had physiological antagonism to Ang II contractions at a lower sensitivity than reported in biochemical studies, and its antagonist activity was partially blocked by Ang II antiserum, suggesting that it is not an antipeptide but an Ang II homologue. The parallel Ang II antipeptide also required high concentrations for physiological inhibition. Its contractile inhibition was not affected by Ang II antiserum and diminished the Ang II contraction at high micromolar concentrations, findings consistent with physicochemical data showing that it is an Ang II complement. The concentration of either peptide required to produce an antagonistic physiological effect was too high to predict any pharmacological usefulness. The parallel antipeptide, however, significantly increased the force of muscle contractions at high nanomolar concentrations, thus displaying a unique dual augmentation/antagonist activity. This antipeptide seems to have highly sequence-specific activity because other similar parallel antipeptides had no activity. The parallel antipeptide augmentation mimics the shift in the Ang II dose-response curve produced in hypertension studies of the slow pressor effect of Ang II and may be useful in deducing the currently unknown cause of the slow pressor effect. It may also have some uses in migraine studies. (Hypertension. 1998;31:854-860.)

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“…This theory is based on the observation that there is a tendency in the genetic code for codons of hydrophilic amino acids to be complemented on the complementary DNA strand by codons for hydrophobic amino acids and vice versa. In spite of ambiguities concerning the universality of the interactions involved in the binding of complementary peptides, the number of reports on complementary peptide pairs has been increasing (2,12,14,15,25,28,30,38). Furthermore, we have suggested that sense and antisense peptide interactions may be involved in the generation and maintenance of the tertiary structure of proteins (2).…”

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confidence: 99%

Inhibition of HIV‐1 Infection by an Intramolecular Antisense Peptide to T20 in gp160

Imai

Okada

2000

Microbiology and Immunology

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Antisense amino acids are amino acids which can be translated from the corresponding anti-codons of a sense amino acid. Antisense peptides encoded by the noncoding DNA strand have a tendency to interact with each other. We have demonstrated that antisense peptide sequences are present intramolecularly, and these may contribute to the folding and maintenance of the tertiary structure of a protein. T20 is a synthetic peptide with an amino acid sequence in the gp41 of HIV-1 and has been demonstrated to be a potent inhibitor of HIV-1 infection. We searched for intramolecular peptide sequences which are antisense to portions of T20. A synthetic peptide (TA-1L) consisting of amino acids 84 to 97 of gp160, which contains an antisense peptide sequence (TA-1) to T20, was shown to inhibit HIV-1,,,B infection of MT-4 cells. Interaction of these antisense peptides could be involved in sustaining HIV-1 infectivity. The TA-1L site, which exists in the Cl domain of gp160, is highly homologous among strains of HIV-1, especially at TA-1 and in the amino acids flanking the C terminus. Although the TA-1 sites of 18 out of 30 HIV-1 strains were antisense to the T20 region, those of the remaining 12 strains, including HIV-1MN, were not. However, TA-1L inhibited infection by HIV-1MN, which has no antisense peptide in T20 corresponding to TA-1, although the inhibitory effect was weaker. TA-1L may thus also interfere with the gp160 interaction with CD4, which has an antisense sequence to TA-1.

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Making sense from antisense: A review of experimental data and developing ideas on sense–antisense peptide recognition

Cited by 53 publications

References 76 publications

Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis

Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis

Augmentation of Aortic Ring Contractions by Angiotensin II Antisense Peptide

Inhibition of HIV‐1 Infection by an Intramolecular Antisense Peptide to T20 in gp160

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