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High affinity binding of conformationally constrained synthetic oligomers to an antigen-specific antibody: Discovery of a diagnostically useful synthetic ligand for murine Type 1 diabetes autoantibodies.

ABSTRACT: 'Antigen surrogates' are synthetic, non-natural molecules that recognize the antigen-binding sites of antibodies. These molecules are of interest as replacements for native antigens as antibody 'capture agents' in ELISA-like assays of potential diagnostic utility, for example when the antibody is indicative of a disease state. Antigen surrogates for disease-related antibodies can be mined from one-bead one-compound (OBOC) libraries by first denuding the library of ligands for antibodies present in the serum of control patients or animals, followed by screening the remainder of the library against serum from individuals with a particular disease of interest. Most of the work in this area has been done with peptoids (oligomers of N-alkylated glycine), which provide antibody ligands with only modest affinity and selectivity. Here, we explore the hypothesis that this is due to the 'floppiness' of the peptoid backbone by creating libraries of peptoid-like molecules that have conformation-restricting structural elements inserted into their backbones. Indeed, we show here that these libraries can provide high affinity and selectivity antigen surrogates and that this much-improved binding is completely dependent on conformational restriction of the oligomer chain.

SUBMITTER: Doran TM

PROVIDER: S-EPMC4607566 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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High affinity binding of conformationally constrained synthetic oligomers to an antigen-specific antibody: Discovery of a diagnostically useful synthetic ligand for murine Type 1 diabetes autoantibodies.

Doran Todd M TM Gao Yu Y Simanski Scott S McEnaney Patrick P Kodadek Thomas T

Bioorganic & medicinal chemistry letters 20150527 21

'Antigen surrogates' are synthetic, non-natural molecules that recognize the antigen-binding sites of antibodies. These molecules are of interest as replacements for native antigens as antibody 'capture agents' in ELISA-like assays of potential diagnostic utility, for example when the antibody is indicative of a disease state. Antigen surrogates for disease-related antibodies can be mined from one-bead one-compound (OBOC) libraries by first denuding the library of ligands for antibodies present ...[more]

PMID: 26067174

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Project description:Coronavirus disease 2019 (COVID-19) is often associated with interstitial pneumonia. However, there is insufficient knowledge on the presence of autoimmune serological markers in patients with COVID-19. We analyzed the presence and role of autoantibodies in patients with COVID-19-associated pneumonia. We prospectively studied 33 consecutive patients with COVID-19, 31 (94%) of whom had interstitial pneumonia, and 25 age-matched and sex-matched patients with fever and/or pneumonia with etiologies other than COVID-19 as the pathological control group. All patients were tested for the presence of antinuclear antibodies (ANAs), anti-antiphospholipid antibodies, and anti-cytoplasmic neutrophil antibodies (ANCAs). Clinical, biochemical, and radiological parameters were also collected. Fifteen of 33 patients (45%) tested positive for at least one autoantibody, including 11 who tested positive for ANAs (33%), 8 who tested positive for anti-cardiolipin antibodies (immunoglobulin (Ig)G and/or IgM; 24%), and 3 who tested positive for anti-β2-glycoprotein antibodies (IgG and/or IgM; 9%). ANCA reactivity was not detected in any patient. Patients that tested positive for auto-antibodies had a significantly more severe prognosis than other patients did: 6 of 15 patients (40%) with auto-antibodies died due to COVID-19 complications during hospitalization, whereas only 1 of 18 patients (5.5%) who did not have auto-antibodies died (P = 0.03). Patients with poor prognosis (death due to COVID-19 complications) had a significantly higher respiratory rate at admission (23 breaths per minute vs. 17 breaths per minute; P = 0.03) and a higher frequency of auto-antibodies (86% vs. 27%; P = 0.008). In conclusion, auto-antibodies are frequently detected in patients with COVID-19 possibly reflecting a pathogenetic role of immune dysregulation. However, given the small number of patients, the association of auto-antibodies with an unfavorable prognosis requires further multicenter studies.

Dataset Information

High affinity binding of conformationally constrained synthetic oligomers to an antigen-specific antibody: Discovery of a diagnostically useful synthetic ligand for murine Type 1 diabetes autoantibodies.

Publications

High affinity binding of conformationally constrained synthetic oligomers to an antigen-specific antibody: Discovery of a diagnostically useful synthetic ligand for murine Type 1 diabetes autoantibodies.

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