We have recently shown that a dominant-negative mutant of CXCL8, dnCXCL8, with increased glycosaminoglycan (GAG) binding affinity and inactivated GPCR signaling function is able to efficiently prevent neutrophil infiltration into murine lungs (Adage et al., 2015). Here we present evidence that chemical PEGylation of dnCXCL8 with 20 kDa and 40 kDa PEG does not significantly interfere with GAG binding affinity, nor does it influence the mutant's disabled chemotaxis function, while it strongly improved bioavailability and serum half-life of the chemokine mutant. In a murine model of lung inflammation, only the 40 kDa PEGylated dnCXCL8 showed a significant reduction of neutrophils in bronchoalveolar lavage (BAL) fluid. In combination with an almost three-fold increase (compared to non-PEGylated dnCXCL8) in plasma half-life after intravenous administration, our results prove that PEGylation of chemokine-derived biologics is an amenable way for the treatment of chronic inflammatory conditions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cyto.2019.154942 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates.
Viruses
January 2025
Department of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization.
View Article and Find Full Text PDFImmunogenicity of HIV-1 mRNA and VLP mRNA Vaccines in Mice.
Vaccines (Basel)
January 2025
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China.
Background: The development of a protective vaccine is critical for conclusively ending the human immunodeficiency virus (HIV) epidemic.
Methods: We constructed nucleotide-modified mRNA vaccines expressing HIV-1 Env and Gag proteins. Env-gag virus-like particles (VLPs) were generated through co-transfection with env and gag mRNA vaccines.
Dynamic G-Quadruplexes in the Rous Sarcoma Virus Genome: Scaffolds for Protein Interaction and Potential Anti-Viral Targets.
Chembiochem
January 2025
Bose Institute - Centenary Campus, Biophysics, P-1/12 CIT Scheme VIIM, Kankurgachi, Centenary Campus, 700054, KOLKATA, INDIA.
The Rous sarcoma virus (RSV) is an onco-retrovirus that infects avian species such as the chicken (Gallus gallus). RSV is the first oncovirus to be described, and the oncogenic activity of this virus is related to the expression of a tyrosine kinase that induces carcinogenic transformation. Interestingly, we have noted that the RSV genome contains various potential G4-forming sequences.
View Article and Find Full Text PDFSulfated Glycosaminoglycans as Inhibitors for Chlamydia Infections: Molecular Weight and Sulfation Dependence.
Macromol Biosci
January 2025
Heinrich- Heine- University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Organic Chemistry and Macromolecular Chemistry, 40204, Düsseldorf, Germany.
Glycosaminoglycans (GAGs) play a pivotal role in pathogen attachment and entry into host cells, where the interaction with GAGs is critical for a diverse range of bacteria and viruses. This study focuses on elucidating the specific interactions between sulfated GAGs and the adhesin OmcB (Outer membrane complex protein B) of Chlamydia species, examining how structural characteristics of GAGs, such as sulfation degree and molecular weight, influence their binding affinity and thereby affect bacterial infectivity. A surface-based binding assay is established to determine the binding constants of OmcB with various GAGs.
View Article and Find Full Text PDFProteomic Identification and Functional Analysis of Reveals Heparin-Binding Proteins.
J Trop Med
January 2025
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Laboratory of Parasite and Vector Biology, Ministry of Public Health, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China.
Glycosaminoglycan (GAG) molecules on the surface of red blood cells play an important regulatory role in the invasion of merozoites of apicomplexan protozoa. Heparan sulfate, a type of GAG molecule, has been identified as an important receptor facilitating the invasion of red blood cells by these parasites. Proteins in the parasite that exhibit strong affinity for heparin may play a pivotal role in this invasion process.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!