{"title":"An Upgraded Solid-Phase Assembly of Chelators (DOTA and NOTA) Enabled Bacterial Uptake Studies of Radiolabeled Peptide.","authors":"Bibekananda Pati, Anuj Kumar, Arnab Chowdhury, Nitesh Mani Tripathi, Vinod Gour, Archana Mukherjee, Anupam Bandyopadhyay","doi":"10.1002/cbic.202400996","DOIUrl":null,"url":null,"abstract":"<p><p>Among popular radio metal chelators, DOTA and NOTA have been remarkably considered in radionuclide therapy and imaging studies due to several advantages in pharmacology. Here, we developed a practical and general method for assembling DOTA and NOTA in the solid phase peptide (pseudo-dilute conditions) using a wide range of solvents with easily accessible and economical feedstocks, which mitigated unprecedented challenges associated with previously reported methods. This upgraded approach enabled an efficient installation of these two chelators on various bioactive peptide sequences. Finally, we assessed the antimicrobial activity of the DOTA- and NOTA-attached Combi peptides to B. subtilis, which was intact. The authenticity of the assembled DOTA framework was assessed by labeling <sup>177</sup>Lu and in vitro bacterial uptake in E. coli and S. aureus. <sup>177</sup>Lu-labeled DOTA-Combi peptide exhibited promising uptake for developing a bacterial infection imaging agent while negligible hemolysis activity even at >200 μM. This contribution will be valued for developing peptide radiopharmaceuticals with operational simplicity and economic approaches.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400996"},"PeriodicalIF":2.6000,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemBioChem","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/cbic.202400996","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Among popular radio metal chelators, DOTA and NOTA have been remarkably considered in radionuclide therapy and imaging studies due to several advantages in pharmacology. Here, we developed a practical and general method for assembling DOTA and NOTA in the solid phase peptide (pseudo-dilute conditions) using a wide range of solvents with easily accessible and economical feedstocks, which mitigated unprecedented challenges associated with previously reported methods. This upgraded approach enabled an efficient installation of these two chelators on various bioactive peptide sequences. Finally, we assessed the antimicrobial activity of the DOTA- and NOTA-attached Combi peptides to B. subtilis, which was intact. The authenticity of the assembled DOTA framework was assessed by labeling 177Lu and in vitro bacterial uptake in E. coli and S. aureus. 177Lu-labeled DOTA-Combi peptide exhibited promising uptake for developing a bacterial infection imaging agent while negligible hemolysis activity even at >200 μM. This contribution will be valued for developing peptide radiopharmaceuticals with operational simplicity and economic approaches.
期刊介绍:
ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).