LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 93

Search options

  1. Article ; Online: Harnessing sortase A transpeptidation for advanced targeted therapeutics and vaccine engineering.

    Obeng, Eugene M / Fulcher, Alex J / Wagstaff, Kylie M

    Biotechnology advances

    2023  Volume 64, Page(s) 108108

    Abstract: The engineering of potent prophylactic and therapeutic complexes has always required careful protein modification techniques with seamless capabilities. In this light, methods that favor unobstructed multivalent targeting and correct antigen ... ...

    Abstract The engineering of potent prophylactic and therapeutic complexes has always required careful protein modification techniques with seamless capabilities. In this light, methods that favor unobstructed multivalent targeting and correct antigen presentations remain essential and very demanding. Sortase A (SrtA) transpeptidation has exhibited these attributes in various settings over the years. However, its applications for engineering avidity-inspired therapeutics and potent vaccines have yet to be significantly noticed, especially in this era where active targeting and multivalent nanomedications are in great demand. This review briefly presents the SrtA enzyme and its associated transpeptidation activity and describes interesting sortase-mediated protein engineering and chemistry approaches for achieving multivalent therapeutic and antigenic responses. The review further highlights advanced applications in targeted delivery systems, multivalent therapeutics, adoptive cellular therapy, and vaccine engineering. These innovations show the potential of sortase-mediated techniques in facilitating the development of simple plug-and-play nanomedicine technologies against recalcitrant diseases and pandemics such as cancer and viral infections.
    MeSH term(s) Bacterial Proteins/metabolism ; Aminoacyltransferases/genetics ; Aminoacyltransferases/chemistry ; Aminoacyltransferases/metabolism ; Cysteine Endopeptidases/chemistry ; Cysteine Endopeptidases/metabolism ; Vaccines
    Chemical Substances sortase A (EC 2.3.2.-) ; Bacterial Proteins ; Aminoacyltransferases (EC 2.3.2.-) ; Cysteine Endopeptidases (EC 3.4.22.-) ; Vaccines
    Language English
    Publishing date 2023-02-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 47165-3
    ISSN 1873-1899 ; 0734-9750
    ISSN (online) 1873-1899
    ISSN 0734-9750
    DOI 10.1016/j.biotechadv.2023.108108
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3730: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: The Nuclear Transporter Importin 13 Can Regulate Stress-Induced Cell Death through the Clusterin/KU70 Axis.

    Gajewska, Katarzyna A / Jans, David A / Wagstaff, Kylie M

    Cells

    2023  Volume 12, Issue 2

    Abstract: The cellular response to environmental stresses, such as heat and oxidative stress, is dependent on extensive trafficking of stress-signalling molecules between the cytoplasm and nucleus, which potentiates stress-activated signalling pathways, eventually ...

    Abstract The cellular response to environmental stresses, such as heat and oxidative stress, is dependent on extensive trafficking of stress-signalling molecules between the cytoplasm and nucleus, which potentiates stress-activated signalling pathways, eventually resulting in cell repair or death. Although Ran-dependent nucleocytoplasmic transport mediated by members of the importin (IPO) super family of nuclear transporters is believed to be responsible for nearly all macromolecular transit between nucleus and cytoplasm, it is paradoxically known to be significantly impaired under conditions of stress. Importin 13 (IPO13) is a unique bidirectional transporter that binds to and releases cargo in a Ran-dependent manner, but in some cases, cargo release from IPO13 is affected by loading of another cargo. To investigate IPO13's role in stress-activated pathways, we performed cell-based screens to identify a multitude of binding partners of IPO13 from human brain, lung, and testes. Analysis of the IPO13 interactome intriguingly indicated more than half of the candidate binding partners to be annotated for roles in stress responses; these included the pro-apoptotic protein nuclear clusterin (nCLU), as well as the nCLU-interacting DNA repair protein KU70. Here, we show, for the first time, that unlike other IPOs which are mislocalised and non-functional, IPO13 continues to translocate between the nucleus and cytoplasm under stress, retaining the capacity to import certain cargoes, such as nCLU, but not export others, such as KU70, as shown by analysis using fluorescence recovery after photobleaching. Importantly, depletion of IPO13 reduces stress-induced import of nCLU and protects against stress-induced cell death, with concomitant protection from DNA damage during stress. Overexpression/FACS experiments demonstrate that nCLU is dependent on IPO13 to trigger stress-induced cell death via apoptosis. Taken together, these results implicate IPO13 as a novel functional nuclear transporter in cellular stress, with a key role thereby in cell fate decision.
    MeSH term(s) Humans ; Clusterin/metabolism ; Cell Nucleus/metabolism ; Cell Death ; Karyopherins/metabolism ; Active Transport, Cell Nucleus
    Chemical Substances Clusterin ; Karyopherins
    Language English
    Publishing date 2023-01-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12020279
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Sortase A transpeptidation produces seamless, unbranched biotinylated nanobodies for multivalent and multifunctional applications.

    Obeng, Eugene M / Steer, David L / Fulcher, Alex J / Wagstaff, Kylie M

    Nanoscale advances

    2023  Volume 5, Issue 8, Page(s) 2251–2260

    Abstract: Exploitation of the biotin-streptavidin interaction for advanced protein engineering is used in many bio-nanotechnology applications. As such, researchers have used diverse techniques involving chemical and enzyme reactions to conjugate biotin to ... ...

    Abstract Exploitation of the biotin-streptavidin interaction for advanced protein engineering is used in many bio-nanotechnology applications. As such, researchers have used diverse techniques involving chemical and enzyme reactions to conjugate biotin to biomolecules of interest for subsequent docking onto streptavidin-associated molecules. Unfortunately, the biotin-streptavidin interaction is susceptible to steric hindrance and conformational malformation, leading to random orientations that ultimately impair the function of the displayed biomolecule. To minimize steric conflicts, we employ sortase A transpeptidation to produce quantitative, seamless, and unbranched nanobody-biotin conjugates for efficient display on streptavidin-associated nanoparticles. We further characterize the protein-nanoparticle complex and demonstrate its usefulness in optical microscopy and multivalent severe acute respiratory syndrome coronavirus (SARS-CoV-2) antigen interaction. The approach reported here provides a template for making novel multivalent and multifunctional protein complexes for avidity-inspired technologies.
    Language English
    Publishing date 2023-03-15
    Publishing country England
    Document type Journal Article
    ISSN 2516-0230
    ISSN (online) 2516-0230
    DOI 10.1039/d3na00014a
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Steric-Deficient Oligoglycine Surrogates Facilitate Multivalent and Bifunctional Nanobody Synthesis via Combined Sortase A Transpeptidation and Click Chemistry.

    Obeng, Eugene M / Steer, David L / Fulcher, Alex / Wagstaff, Kylie M

    Bioconjugate chemistry

    2023  Volume 34, Issue 9, Page(s) 1667–1678

    Abstract: Conferring multifunctional properties to proteins via enzymatic approaches has greatly facilitated recent progress in protein nanotechnology. In this regard, sortase (Srt) A transpeptidation has facilitated many of these developments due to its ... ...

    Abstract Conferring multifunctional properties to proteins via enzymatic approaches has greatly facilitated recent progress in protein nanotechnology. In this regard, sortase (Srt) A transpeptidation has facilitated many of these developments due to its exceptional specificity, mild reaction conditions, and complementation with other bioorthogonal techniques, such as click chemistry. In most of these developments, Srt A is used to seamlessly tether oligoglycine-containing molecules to a protein of interest that is equipped with the enzyme's recognition sequence, LPXTG. However, the dependence on oligoglycine attacking nucleophiles and the associated cost of certain derivatives (e.g., cyclooctyne) limit the utility of this approach to lab-scale applications only. Thus, the quest to identify appropriate alternatives and understand their effectiveness remains an important area of research. This study identifies that steric and nucleophilicity-associated effects influence Srt A transpeptidation when two oligoglycine surrogates were examined. The approach was further used in complementation with click chemistry to synthesize bivalent and bifunctional nanobody conjugates for application in epithelial growth factor receptor targeting. The overall technique and tools developed here may facilitate the advancement of future nanotechnologies.
    MeSH term(s) Click Chemistry ; Bacterial Proteins/chemistry ; Aminoacyltransferases/metabolism ; Cysteine Endopeptidases/metabolism
    Chemical Substances sortase A (EC 2.3.2.-) ; Bacterial Proteins ; Aminoacyltransferases (EC 2.3.2.-) ; Cysteine Endopeptidases (EC 3.4.22.-)
    Language English
    Publishing date 2023-08-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1024041-x
    ISSN 1520-4812 ; 1043-1802
    ISSN (online) 1520-4812
    ISSN 1043-1802
    DOI 10.1021/acs.bioconjchem.3c00319
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3400: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article: Internalized Functional DNA Aptamers as Alternative Cancer Therapies.

    Marshall, Morgan L / Wagstaff, Kylie M

    Frontiers in pharmacology

    2020  Volume 11, Page(s) 1115

    Abstract: Despite major advances, cancer remains one of the largest burdens of disease worldwide. One reason behind this is that killing tumor cells without affecting healthy surrounding tissue remains a largely elusive prospect, despite the widespread ... ...

    Abstract Despite major advances, cancer remains one of the largest burdens of disease worldwide. One reason behind this is that killing tumor cells without affecting healthy surrounding tissue remains a largely elusive prospect, despite the widespread availability of cytotoxic chemotherapeutic agents. To meet these modern healthcare requirements, it is essential to develop precision therapeutics that minimise off-target side-effects for various cancer types. To this end, highly specific molecular targeting agents against cancer are of great interest. These agents may work by targeting intracellular signalling pathways following receptor binding, or
    Language English
    Publishing date 2020-07-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2020.01115
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?

    Jans, David A / Wagstaff, Kylie M

    Cells

    2020  Volume 9, Issue 9

    Abstract: The small molecule macrocyclic lactone ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its apparent exciting potential as an antiviral. It was identified ... ...

    Abstract The small molecule macrocyclic lactone ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its apparent exciting potential as an antiviral. It was identified in a high-throughput chemical screen as inhibiting recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host heterodimeric importin (IMP) α/β1 complex, and has since been shown to bind directly to IMPα to induce conformational changes that prevent its normal function in mediating nuclear import of key viral and host proteins. Excitingly, cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Phase III human clinical trials have been completed for DENV, with >50 trials currently in progress worldwide for SARS-CoV-2. This mini-review discusses the case for ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; Betacoronavirus/drug effects ; COVID-19 ; Cell Line ; Chlorocebus aethiops ; Coronavirus Infections/drug therapy ; Dengue/drug therapy ; Dengue Virus/drug effects ; HIV Infections/drug therapy ; HIV Integrase/drug effects ; HIV Integrase Inhibitors/pharmacology ; HIV-1/drug effects ; Humans ; Ivermectin/pharmacology ; Pandemics ; Pneumonia, Viral/drug therapy ; SARS-CoV-2 ; Vero Cells ; Zika Virus/drug effects ; Zika Virus Infection/drug therapy
    Chemical Substances Antiviral Agents ; HIV Integrase Inhibitors ; Ivermectin (70288-86-7) ; HIV Integrase (EC 2.7.7.-)
    Keywords covid19
    Language English
    Publishing date 2020-09-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9092100
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?

    Jans, David A / Wagstaff, Kylie M

    Biochemical and biophysical research communications

    2020  Volume 538, Page(s) 163–172

    Abstract: FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an ... ...

    Abstract FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) α/β1 heterodimer, and recently demonstrated its ability to bind directly to IMPα to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins. Cell culture experiments have shown robust antiviral action towards a whole range of viruses, including HIV-1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Close to 70 clinical trials are currently in progress worldwide for SARS-CoV-2. Although few of these studies have been completed, the results that are available, as well as those from observational/retrospective studies, indicate clinical benefit. Here we discuss the case for ivermectin as a host-directed broad-spectrum antiviral agent, including for SARS-CoV-2.
    MeSH term(s) Antiparasitic Agents/pharmacology ; Antiparasitic Agents/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Humans ; Ivermectin/pharmacology ; Ivermectin/therapeutic use ; SARS-CoV-2/drug effects ; alpha Karyopherins/antagonists & inhibitors
    Chemical Substances Antiparasitic Agents ; Antiviral Agents ; alpha Karyopherins ; Ivermectin (70288-86-7)
    Language English
    Publishing date 2020-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2020.10.042
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 116: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: Transcriptomic profile dataset of embryonic stem cells (Wild-type and IPO13-Knock Out) with and without oxidative stress.

    Gajewska, Katarzyna A / Ramialison, Mirana / Wagstaff, Kylie M / Jans, David A

    Data in brief

    2022  Volume 42, Page(s) 108099

    Abstract: The transcriptional response to cellular stress relies upon trafficking of regulators of transcription between the nuclear and cytoplasmic compartments, which occurs through action of members of the importin (IPO) superfamily. As a result of stresses ... ...

    Abstract The transcriptional response to cellular stress relies upon trafficking of regulators of transcription between the nuclear and cytoplasmic compartments, which occurs through action of members of the importin (IPO) superfamily. As a result of stresses such as oxidative or osmotic stress, one consequence is that importins become mislocalised, leading to inhibition of conventional nuclear transport. Here, we examine IPO13, which has a number of nonconventional characteristics, in the context of cell stress. We used Next Generation RNA Sequencing using the Illumina platform to compare the transcriptomes of Wild-type (WT) and IPO13-Knockout (KO) mouse embryonic stem cells in the absence and presence of oxidative stress. Differences in the mRNA expression profiles were observed between the cell lines in the absence and in the presence of stress. This data will be a key resource to enable characterization of the contribution of nuclear transporter IPO13 to cellular transcription in the absence and presence of oxidative stress, as well as more broadly, in the study of stem cell biology and effect of stress on embryonic stem cell transcription.
    Language English
    Publishing date 2022-03-28
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2786545-9
    ISSN 2352-3409 ; 2352-3409
    ISSN (online) 2352-3409
    ISSN 2352-3409
    DOI 10.1016/j.dib.2022.108099
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2?

    Jans, David A. / Wagstaff, Kylie M.

    Biochemical and Biophysical Research Communications ; ISSN 0006-291X

    2020  

    Keywords Biophysics ; Cell Biology ; Biochemistry ; Molecular Biology ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    DOI 10.1016/j.bbrc.2020.10.042
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top