Marco Bertolini, Lorena Mendive-Tapia, Ouldouz Ghashghaei, Abigail Reese, Charles Lochenie, Anna M. Schoepf, Miquel Sintes, Karolina Tokarczyk, Zandile Nare, Andrew D. Scott, Stephen R. Knight, Advait R. Aithal, Amit Sachdeva, Rodolfo Lavilla* and Marc Vendrell*,
{"title":"免疫亲和素的非过扰性荧光标记可实现免疫抑制剂的免清洗检测","authors":"Marco Bertolini, Lorena Mendive-Tapia, Ouldouz Ghashghaei, Abigail Reese, Charles Lochenie, Anna M. Schoepf, Miquel Sintes, Karolina Tokarczyk, Zandile Nare, Andrew D. Scott, Stephen R. Knight, Advait R. Aithal, Amit Sachdeva, Rodolfo Lavilla* and Marc Vendrell*, ","doi":"10.1021/acscentsci.3c01590","DOIUrl":null,"url":null,"abstract":"<p >Immunosuppressants are clinically approved drugs to treat the potential rejection of transplanted organs and require frequent monitoring due to their narrow therapeutic window. Immunophilins are small proteins that bind immunosuppressants with high affinity, yet there are no examples of fluorogenic immunophilins and their potential application as optical biosensors for immunosuppressive drugs in clinical biosamples. In the present work, we designed novel diazonium BODIPY salts for the site-specific labeling of tyrosine residues in peptides via solid-phase synthesis as well as for late-stage functionalization of whole recombinant proteins. After the optimization of a straightforward one-step labeling procedure for immunophilins PPIA and FKBP12, we demonstrated the application of a fluorogenic analogue of FKBP12 for the selective detection of the immunosuppressant drug tacrolimus, including experiments in urine samples from patients with functioning renal transplants. This chemical methodology opens new avenues to rationally design wash-free immunophilin-based biosensors for rapid therapeutic drug monitoring.</p><p >We describe diazonium BODIPYs for the straightforward labeling of Tyr-containing peptides and whole proteins and the first fluorogenic analogue of immunophilin FKBP12 for the wash-free detection of tacrolimus in clinical biosamples.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":12.7000,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.3c01590","citationCount":"0","resultStr":"{\"title\":\"Nonperturbative Fluorogenic Labeling of Immunophilins Enables the Wash-free Detection of Immunosuppressants\",\"authors\":\"Marco Bertolini, Lorena Mendive-Tapia, Ouldouz Ghashghaei, Abigail Reese, Charles Lochenie, Anna M. Schoepf, Miquel Sintes, Karolina Tokarczyk, Zandile Nare, Andrew D. Scott, Stephen R. Knight, Advait R. Aithal, Amit Sachdeva, Rodolfo Lavilla* and Marc Vendrell*, \",\"doi\":\"10.1021/acscentsci.3c01590\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Immunosuppressants are clinically approved drugs to treat the potential rejection of transplanted organs and require frequent monitoring due to their narrow therapeutic window. Immunophilins are small proteins that bind immunosuppressants with high affinity, yet there are no examples of fluorogenic immunophilins and their potential application as optical biosensors for immunosuppressive drugs in clinical biosamples. In the present work, we designed novel diazonium BODIPY salts for the site-specific labeling of tyrosine residues in peptides via solid-phase synthesis as well as for late-stage functionalization of whole recombinant proteins. After the optimization of a straightforward one-step labeling procedure for immunophilins PPIA and FKBP12, we demonstrated the application of a fluorogenic analogue of FKBP12 for the selective detection of the immunosuppressant drug tacrolimus, including experiments in urine samples from patients with functioning renal transplants. This chemical methodology opens new avenues to rationally design wash-free immunophilin-based biosensors for rapid therapeutic drug monitoring.</p><p >We describe diazonium BODIPYs for the straightforward labeling of Tyr-containing peptides and whole proteins and the first fluorogenic analogue of immunophilin FKBP12 for the wash-free detection of tacrolimus in clinical biosamples.</p>\",\"PeriodicalId\":10,\"journal\":{\"name\":\"ACS Central Science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.7000,\"publicationDate\":\"2024-03-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.3c01590\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Central Science\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acscentsci.3c01590\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Central Science","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acscentsci.3c01590","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Nonperturbative Fluorogenic Labeling of Immunophilins Enables the Wash-free Detection of Immunosuppressants
Immunosuppressants are clinically approved drugs to treat the potential rejection of transplanted organs and require frequent monitoring due to their narrow therapeutic window. Immunophilins are small proteins that bind immunosuppressants with high affinity, yet there are no examples of fluorogenic immunophilins and their potential application as optical biosensors for immunosuppressive drugs in clinical biosamples. In the present work, we designed novel diazonium BODIPY salts for the site-specific labeling of tyrosine residues in peptides via solid-phase synthesis as well as for late-stage functionalization of whole recombinant proteins. After the optimization of a straightforward one-step labeling procedure for immunophilins PPIA and FKBP12, we demonstrated the application of a fluorogenic analogue of FKBP12 for the selective detection of the immunosuppressant drug tacrolimus, including experiments in urine samples from patients with functioning renal transplants. This chemical methodology opens new avenues to rationally design wash-free immunophilin-based biosensors for rapid therapeutic drug monitoring.
We describe diazonium BODIPYs for the straightforward labeling of Tyr-containing peptides and whole proteins and the first fluorogenic analogue of immunophilin FKBP12 for the wash-free detection of tacrolimus in clinical biosamples.
期刊介绍:
ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.