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  1. Article: Nonperturbative Fluorogenic Labeling of Immunophilins Enables the Wash-free Detection of Immunosuppressants.

    Bertolini, Marco / Mendive-Tapia, Lorena / Ghashghaei, Ouldouz / Reese, Abigail / Lochenie, Charles / Schoepf, Anna M / Sintes, Miquel / Tokarczyk, Karolina / Nare, Zandile / Scott, Andrew D / Knight, Stephen R / Aithal, Advait R / Sachdeva, Amit / Lavilla, Rodolfo / Vendrell, Marc

    ACS central science

    2024  Volume 10, Issue 5, Page(s) 969–977

    Abstract: 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 ... ...

    Abstract 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.
    Language English
    Publishing date 2024-03-18
    Publishing country United States
    Document type Journal Article
    ISSN 2374-7943
    ISSN 2374-7943
    DOI 10.1021/acscentsci.3c01590
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses.

    Tushir, Sheetal / Kamanna, Sathisha / Nath, Sujith S / Bhat, Aishwarya / Rose, Steffimol / Aithal, Advait R / Tatu, Utpal

    Journal of proteome research

    2021  Volume 20, Issue 3, Page(s) 1591–1601

    Abstract: A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic ... ...

    Abstract A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic analysis using next-generation sequencing (NGS) and mass spectrometry on nasopharyngeal swabs of COVID-19 patients to examine the clinical genome and proteome. Our study confirms the mutability of SARS-CoV-2 showing multiple single-nucleotide polymorphisms. NGS analysis detected 27 mutations, of which 14 are synonymous, 11 are missense, and 2 are extragenic in nature. Phylogenetic analysis of SARS-CoV-2 isolates indicated their close relation to a Bangladesh isolate and multiple origins of isolates within the country. Our proteomic analysis, for the first time, identified 13 different SARS-CoV-2 proteins from the clinical swabs. Of the total 41 peptides captured by high-resolution mass spectrometry, 8 matched to nucleocapsid protein, 2 to ORF9b, and 1 to spike glycoprotein and ORF3a, with remaining peptides mapping to ORF1ab polyprotein. Additionally, host proteome analysis revealed several key host proteins to be uniquely expressed in COVID-19 patients. Pathway analysis of these proteins points toward modulation in immune response, especially involving neutrophil and IL-12-mediated signaling. Besides revealing the aspects of host-virus pathogenesis, our study opens new avenues to develop better diagnostic markers and therapeutic approaches.
    MeSH term(s) COVID-19/virology ; Coronavirus Nucleocapsid Proteins/genetics ; Genome, Viral ; Genomics ; High-Throughput Nucleotide Sequencing ; Host Microbial Interactions/genetics ; Host Microbial Interactions/physiology ; Humans ; Mutation ; Pandemics ; Phosphoproteins/genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Polyproteins/genetics ; Proteome ; Proteomics ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/genetics ; Viral Proteins/genetics ; Viroporin Proteins/genetics
    Chemical Substances Coronavirus Nucleocapsid Proteins ; ORF1ab polyprotein, SARS-CoV-2 ; ORF3a protein, SARS-CoV-2 ; Phosphoproteins ; Polyproteins ; Proteome ; Spike Glycoprotein, Coronavirus ; Viral Proteins ; Viroporin Proteins ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-02-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.0c00808
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6189: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Proteo-genomic analysis of SARS-CoV-2: A clinical landscape of SNPs, COVID-19 proteome and host responses

    Tushir, Sheetal / Kamanna, Sathisha / Nath, Sujith S / Bhat, Aishwarya / Rose, Steffimol / Aithal, Advait R / Tatu, Utpal

    medRxiv

    Abstract: A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic analysis using next generation ... ...

    Abstract A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic analysis using next generation sequencing (NGS) and mass-spectrometry on nasopharyngeal swabs of COVID-19 patients to examine clinical genome and proteome. Our study confirms the hyper mutability of SARS-CoV-2 showing multiple SNPs. NGS analysis detected 27 mutations of which 14 are synonymous, 11 are missense and 2 are extragenic in nature. Phylogenetic analysis of SARS-CoV-2 isolates indicated their close relation to Bangladesh isolate and multiple origins of isolates within a country. Our proteomic analysis, for the first time identified 13 different SARS-CoV-2 proteins from the clinical swabs. Of the total 41 peptides captured by HRMS, 8 matched to nucleocapsid protein, 2 to ORF9b, 1 to spike glycoprotein and ORF3a, with remaining mapping to ORF1ab polyprotein. Additionally, host proteome analysis revealed several key host proteins to be uniquely expressed in COVID-19 patients. Pathway analysis of these proteins points towards modulation in immune response, especially involving neutrophil and IL-12 mediated signaling. Besides revealing the aspects of host-virus pathogenesis, our study opens new avenues to develop better diagnostic markers and therapeutics.
    Keywords covid19
    Language English
    Publishing date 2020-11-30
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.11.27.20237032
    Database COVID19

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