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Pharmaceutics
Special Issues
Protein Modification and Its Intracellular Delivery for Therapeutic Purposes
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Protein Modification and Its Intracellular Delivery for Therapeutic Purposes

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (20 November 2022) | Viewed by 9090

Special Issue Editors

Dr. Maria Francesca Baietti

E-Mail Website
Guest Editor
TRACE, Department of Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
Interests: cancer biology; protein modification; intracellular signaling; extracellular vesicles; preclinical research
Dr. Raj Nayan Sewduth

E-Mail Website
Guest Editor
VIB, Department of Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
Interests: novel anti-cancer agents; protein modification; drug discovery; disease modeling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There are more than 400 different types of posttranslational modifications (PTMs) that affect many aspects of protein functions, such as stability, trafficking or aggregation. Such modifications regulate crucial molecular mechanisms that regulate diverse cellular processes. Disruption in protein modification causes dysfunction of vital biological processes and is implicated in various diseases, such as cancer or neurological diseases. Drugs inducing protein degradation or aggregation have emerged as a novel therapeutic strategy in drug development. Recent evidence demonstrates that such approaches are alternatives to traditional approaches. However, these approaches present the challenge of intracellular delivery, as they request novel targeting approaches.

Dr. Maria Francesca Baietti
Dr. Raj Nayan Sewduth
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • protein modification
  • intracellular trafficking
  • therapy
  • drug design

Published Papers (4 papers)

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Research

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20 pages, 3428 KiB  
Article
Dimeric Lectin Chimeras as Novel Candidates for Gb3-Mediated Transcytotic Drug Delivery through Cellular Barriers
by Maokai Xu, Maria Antonova, Pavel Salavei, Katharina Illek, Ana Valeria Meléndez, Ramin Omidvar, Roland Thuenauer, Olga Makshakova and Winfried Römer
Pharmaceutics 2023, 15(1), 225; https://doi.org/10.3390/pharmaceutics15010225 - 09 Jan 2023
Viewed by 1370
Abstract
Receptor-mediated transcytosis is an elegant and promising strategy for drug delivery across biological barriers. Here, we describe a novel ligand–receptor pair based on a dimeric, engineered derivative of the Pseudomonas aeruginosa lectin LecA, here termed Di-LecA, and the host cell glycosphingolipid Gb3. We [...] Read more.
Receptor-mediated transcytosis is an elegant and promising strategy for drug delivery across biological barriers. Here, we describe a novel ligand–receptor pair based on a dimeric, engineered derivative of the Pseudomonas aeruginosa lectin LecA, here termed Di-LecA, and the host cell glycosphingolipid Gb3. We characterized the trafficking kinetics and transcytosis efficiencies in polarized Gb3-positive and -negative MDCK cells using mainly immunofluorescence in combination with confocal microscopy. To evaluate the delivery capacity of dimeric LecA chimeras, EGFP was chosen as a fluorescent model protein representing macromolecules, such as antibody fragments, and fused to either the N- or C-terminus of monomeric LecA using recombinant DNA technology. Both LecA/EGFP fusion proteins crossed cellular monolayers in vitro. Of note, the conjugate with EGFP at the N-terminus of LecA (EGFP-LecA) showed a higher release rate than the conjugate with EGFP at the C-terminus (LecA-EGFP). Based on molecular dynamics simulations and cross-linking studies of giant unilamellar vesicles, we speculate that EGFP-LecA tends to be a dimer while LecA-EGFP forms a tetramer. Overall, we confidently propose the dimeric LecA chimeras as transcytotic drug delivery tools through Gb3-positive cellular barriers for future in vivo tests. Full article
(This article belongs to the Special Issue Protein Modification and Its Intracellular Delivery for Therapeutic Purposes)
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10 pages, 2743 KiB  
Article
Protein Modification Employing Non-Canonical Amino Acids to Prepare SUMOylation Detecting Bioconjugates
by Alexander C. Williard, Hannah J. Switzer, Christina A. Howard, Rui Yin, Brent L. Russell, Ritwik Sanyal, Shaun Yu, Trinity M. Myers, Brian M. Flood, Oliver Kerscher and Douglas D. Young
Pharmaceutics 2022, 14(12), 2826; https://doi.org/10.3390/pharmaceutics14122826 - 16 Dec 2022
Viewed by 2042
Abstract
Protein modification with non-canonical amino acids (ncAAs) represents a useful technology to afford homogenous samples of bioconjugates with site-specific modification. This technique can be directly applied to the detection of aberrant SUMOylation patterns, which are often indicative of disease states. Modified SUMO-trapping proteins, [...] Read more.
Protein modification with non-canonical amino acids (ncAAs) represents a useful technology to afford homogenous samples of bioconjugates with site-specific modification. This technique can be directly applied to the detection of aberrant SUMOylation patterns, which are often indicative of disease states. Modified SUMO-trapping proteins, consisting of a catalytically inactive ULP1 fragment (UTAG) fused to the maltose-binding protein MBP, are useful reagents for the binding and labeling of SUMOylated proteins. Mutation of this UTAG fusion protein to facilitate amber suppression technologies for the genetic incorporation of ncAAs was assessed to provide a functional handle for modification. Ultimately, two sites in the maltose-binding protein (MBP) fusion were identified as ideal for incorporation and bioconjugation without perturbation to the SUMO-trapping ability of the UTAG protein. This functionality was then employed to label SUMOylated proteins in HeLa cells and demonstrate their enrichment in the nucleus. This modified UTAG-MBP-ncAA protein has far-reaching applications for both diagnostics and therapeutics. Full article
(This article belongs to the Special Issue Protein Modification and Its Intracellular Delivery for Therapeutic Purposes)
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Review

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13 pages, 641 KiB  
Review
Novel Therapeutic Approaches Targeting Post-Translational Modifications in Lung Cancer
by Maria Francesca Baietti and Raj Nayan Sewduth
Pharmaceutics 2023, 15(1), 206; https://doi.org/10.3390/pharmaceutics15010206 - 06 Jan 2023
Cited by 3 | Viewed by 2467
Abstract
Lung cancer is one of the most common cancers worldwide. It consists of two different subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Despite novel therapeutic options such as immunotherapy, only 20% of lung cancer patients survive the disease [...] Read more.
Lung cancer is one of the most common cancers worldwide. It consists of two different subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Despite novel therapeutic options such as immunotherapy, only 20% of lung cancer patients survive the disease after five years. This low survival rate is due to acquired drug resistance and severe off-target effects caused by currently used therapies. Identification and development of novel and targeted therapeutic approaches are urgently required to improve the standard of care for lung cancer patients. Here, we describe the recent development of novel drug-delivery approaches, such as adenovirus, lipid nanoparticles, and PROTACs, that have been tested in clinical trials and experimentally in the context of fundamental research. These different options show that it is now possible to target protein kinases, phosphatases, ubiquitin ligases, or protein modifications directly in lung cancer to block disease progression. Furthermore, the recent acceptance of RNA vaccines using lipid nanoparticles has further revealed therapeutic options that could be combined with chemo-/immunotherapies to improve current lung cancer therapies. This review aims to compare recent advances in the pharmaceutical research field for the development of technologies targeting post-translational modifications or protein modifiers involved in the tumorigenesis of lung cancer. Full article
(This article belongs to the Special Issue Protein Modification and Its Intracellular Delivery for Therapeutic Purposes)
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25 pages, 1741 KiB  
Review
“Targeting Design” of Nanoparticles in Tumor Therapy
by Tingting Yang, Jingming Zhai, Dong Hu, Ruyue Yang, Guidan Wang, Yuanpei Li and Gaofeng Liang
Pharmaceutics 2022, 14(9), 1919; https://doi.org/10.3390/pharmaceutics14091919 - 11 Sep 2022
Cited by 13 | Viewed by 2305
Abstract
Tumor-targeted therapy based on nanoparticles is a popular research direction in the biomedical field. After decades of research and development, both the passive targeting ability of the inherent properties of NPs and the active targeting based on ligand receptor interaction have gained deeper [...] Read more.
Tumor-targeted therapy based on nanoparticles is a popular research direction in the biomedical field. After decades of research and development, both the passive targeting ability of the inherent properties of NPs and the active targeting based on ligand receptor interaction have gained deeper understanding. Unfortunately, most targeted delivery strategies are still in the preclinical trial stage, so it is necessary to further study the biological fate of particles in vivo and the interaction mechanism with tumors. This article reviews different targeted delivery strategies based on NPs, and focuses on the physical and chemical properties of NPs (size, morphology, surface and intrinsic properties), ligands (binding number/force, activity and species) and receptors (endocytosis, distribution and recycling) and other factors that affect particle targeting. The limitations and solutions of these factors are further discussed, and a variety of new targeting schemes are introduced, hoping to provide guidance for future targeting design and achieve the purpose of rapid transformation of targeted particles into clinical application. Full article
(This article belongs to the Special Issue Protein Modification and Its Intracellular Delivery for Therapeutic Purposes)
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