A Novel Reagent for Radioiodine Labeling of New Chemical Entities (NCEs) and Biomolecules

Kumar, Krishan; Woolum, Karen

doi:10.3390/molecules26144344

Cited by 16 publications

(11 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Iodogen was used as an oxidizing agent to facilitate direct conjugation of positive radioiodine species (I + ) into tyrosine and/or histidine residues in the IgY anti-RBD spike SARS-CoV-2 structure. In large biomolecules, such as proteins and antibodies, the primary site responsible for iodination is tyrosine residues; however, in more basic reaction conditions (pH exceeds 8.5), the secondary site on the histidine residues (imidazole ring) is favored (Figure 3) [38,39]. Purification using SEC gave a radiochemical purity of 99.8 ± 0.3 (n = 3) (TLC analysis) (Figure 4A).…”

Section: Radiolabelingmentioning

confidence: 99%

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

Wongso¹,

Mahendra²,

Arnafia³

et al. 2022

Vaccines

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) has become a substantial threat to the international health sector and the global economy. As of 26 December 2021, the number of mortalities resulting from COVID-19 exceeded 5.3 million worldwide. The absence of an effective non-vaccine treatment has prompted the quest for prophylactic agents that can be used to combat COVID-19. This study presents the feasibility of chicken egg yolk antibody (IgY) anti-receptor-binding domain (RBD) spike SARS-CoV-2 as a strong candidate to neutralize the virus for application in passive immunization. For the purpose of preclinical studies, we radiolabeled IgY anti-RBD spike SARS-CoV-2 with radionuclide iodine-131. This allowed us to evaluate several biological characteristics of IgY in vitro, in vivo, and ex vivo. The preclinical data suggest that IgY anti-RBD spike SARS-CoV-2 could specifically bind to the SARS-CoV-2 antigens; however, little uptake was observed in normal cells (MRC-5) (<2%). Furthermore, the ex vivo biodistribution study revealed that IgY predominantly accumulated in the trachea of normal mice compared to other organs. We also found that IgY possessed a good safety profile when used as an intranasal agent. Taken together, we propose that IgY anti-RBD spike SARS-CoV-2 has the potential for application in passive immunization against COVID-19.

show abstract

Section: Radiolabelingmentioning

confidence: 99%

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

Wongso¹,

Mahendra²,

Arnafia³

et al. 2022

Vaccines

View full text Add to dashboard Cite

show abstract

“…For this purpose, the reaction conditions of iodination at the His residue of NMS were optimized to synthesize an iodinated precursor. The peptide was treated at pH 5 and pH 10 with sodium iodide in four different oxidizing agents, namely, chloramine-T, Iodo-Beads (polymer-supported version of chloramine-T), iodogen, and the recently described chloramine oxidant . The highest iodine incorporation was obtained using chloramine-T at pH 10 with 35% 127 I 1 and 65% 127 I 2 (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…Fifty nine micrograms (0.40 μmol, 3 equiv) of sodium iodide, dissolved in 3.7 μL of PBS at pH 7.3, was added. Four equivalents (0.53 μmol) of oxidation agents chloramine-T (0.12 μg in 8.5 μL of PBS at pH 7.3), iodogen (0.23 μg in 11.8 μL of PBS at pH 7.3), and freshly prepared chloramine according to a published procedure 24 was added. When using polymer-bound chloramine-T (loading: 0.2 mmol/g), a single bead with a weight of 15 mg was used, which corresponds to an amount of substance of about 3 μmol (22.7 equiv).…”

Section: Methodsmentioning

confidence: 99%

“…The peptide was treated at pH 5 and pH 10 with sodium iodide in four different oxidizing agents, namely, chloramine-T, Iodo-Beads (polymer-supported version of chloramine-T), iodogen, and the recently described chloramine oxidant. 24 The highest iodine incorporation was obtained using chloramine-T at pH 10 with 35% 127 I 1 and 65% 127 I 2 (Table 1). The catalytic exchange of iodine-127 to tritium is described in the literature exclusively on iodinated Tyr residues, although for the tritium labeling approach of peptides, direct iodination on His is also mentioned.…”

Section: ■ Considerations For Tritiating Peptidesmentioning

confidence: 96%

See 1 more Smart Citation

Tritium Labeling of Neuromedin S by Conjugation with [³H]N-Succinimidyl Propionate

et al. 2023

View full text Add to dashboard Cite

The human neuropeptide neuromedin S (NMS) consists of 33 amino acids. The introduction of tritium atoms into NMS has not been described so far. This represents a gap for using [ 3 H]NMS in radioreceptor binding assays or in tracking and monitoring their metabolic pathway. Two approaches for the incorporation of tritium into NMS were explored in this study: (1) halogenation at the His-18 residue followed by catalyzed iodine-127/tritium exchange and (2) conjugation of tritiated N -succinimidyl-[2,3- 3 H 3 ]propionate ([ 3 H]NSP) to at least one of the three available primary amines of amino acids Ile-1, Lys-15, and Lys-16 in the peptide sequence. Although iodination of histidine was achieved, subsequent iodine-127/deuterium exchange was unsuccessful. Derivatization at the three possible amino positions in the peptide using nonradioactive NSP resulted in a mixture of unconjugated NSM and 1- to 3-conjugations at different amino acids in the peptide sequence. Each labeling position in the mixture was assigned following detailed LC–MS/MS analysis. After separating the mixture, it was shown in an in vitro fluorometric imaging plate reader (FLIPR) and in a competitive binding assay that the propionyl-modified NMS derivatives were comparable to the unlabeled NMS, regardless of the degree of labeling and the labeling position(s). A molecular simulation with NMS in the binding pocket of the protein neuromedin U receptor 2 (NMUR 2 ) confirmed that the possible labeling positions are located outside the binding region of NMUR 2 . Tritium labeling was achieved at the N-terminal Ile-1 using [ 3 H]NSP in 7% yield with a radiochemical purity of >95% and a molar activity of 90 Ci/mmol. This approach provides access to tritiated NMS and enables new investigations to characterize NMS or corresponding NMS ligands.

show abstract

“…Some radionuclides such as iodine-131, iodine-125, technetium-99m, fluorine-18, gallium-68, and carbon-11 have been used for labeling numerous active compounds for their in vitro and in vivo biomedical applications [6,[8][9][10][11][12][13]. Among them, radioiodines are very useful for labeling bioactive molecules containing phenol or imidazole groups [14].…”

Section: Introduction mentioning

confidence: 99%

Efficient and Practical Radiosynthesis of Novel [131I]-Xanthine and [131I]-Hypoxanthine

Wongso¹,

Nuraeni²,

Rosyidiah³

2022

Atom Indo.

View full text Add to dashboard Cite

Natural products (NPs) have been the basis for the discovery and development of pharmacologically relevant drug-related molecules, including radiopharmaceuticals. Xanthine (3,7-dihydropurine-2,6-dione) and hypoxanthine (1,9-dihydro-6H-purin-6-one) are purine-based natural heterocyclic alkaloids that are generally found in some plants, animals, and the human body (e.g., muscle tissue, blood, and urine). The purpose of this study was to label xanthine and hypoxanthine with radioactive iodine-131 (a theranostic radionuclide) by a direct labeling method using chloramine-T as an oxidizing agent. Several experiments were performed to optimize the labeling efficiency by changing reaction conditions, including the ratio of starting material and chloramine-T, pH, solvent, temperature, and reaction time. Overall, labeling at acidic conditions in dimethyl sulfoxide (DMSO) resulted in considerable low radiochemical yields (RCYs) (< 4.0 %), and therefore the focus was shifted to exploit the alkaline reaction conditions.The optimized reaction condition: pH (10.5-11.0), xanthine:chloramine-T ratio (1:2), reaction temperature (27 ºC), and reaction time (30 min), provided [ 131 I]-xanthine with a RCY of 65.8 ± 0.1 %. After purification with extraction using chloroform (CHCl 2 ), the radiochemical purity (RCP) of 95.1 % was achieved, as indicated by radio-thin layer chromatography (radio-TLC) analysis. In addition, the labeling of hypoxanthine was accomplished in a maximum 60.3 ± 0.2 % RCY, and after purification a RCP of 94.2 % was obtained. The present results provide an efficient and practical labeling method for xanthine and hypoxanthine with iodine-131, suggesting that these radiolabeled compounds can be further investigated in in vitro and in vivo studies for their theranostics potential.

show abstract

A Novel Reagent for Radioiodine Labeling of New Chemical Entities (NCEs) and Biomolecules

Cited by 16 publications

References 34 publications

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

Tritium Labeling of Neuromedin S by Conjugation with [³H]N-Succinimidyl Propionate

Efficient and Practical Radiosynthesis of Novel [131I]-Xanthine and [131I]-Hypoxanthine

Contact Info

Product

Resources

About

A Novel Reagent for Radioiodine Labeling of New Chemical Entities (NCEs) and Biomolecules

Cited by 16 publications

References 34 publications

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

Preclinical Evaluation of Chicken Egg Yolk Antibody (IgY) Anti-RBD Spike SARS-CoV-2—A Candidate for Passive Immunization against COVID-19

Tritium Labeling of Neuromedin S by Conjugation with [3H]N-Succinimidyl Propionate

Efficient and Practical Radiosynthesis of Novel [131I]-Xanthine and [131I]-Hypoxanthine

Contact Info

Product

Resources

About

Tritium Labeling of Neuromedin S by Conjugation with [³H]N-Succinimidyl Propionate