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Polyvalent Hybrid Virus-Like Nanoparticles with Displayed Heparin Antagonist Peptides.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2018 Aug 06; Vol. 15 (8), pp. 2997-3004. Date of Electronic Publication: 2018 Jul 02. - Publication Year :
- 2018
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Abstract
- The potential applications for nanomaterials continue to grow as new materials are developed and environmental and safety concerns are more adequately addressed. In particular, virus-like particles (VLPs) have myriad applications in medicine and biology, exploiting both the reliable, symmetric self-assembly mechanism and the ability to take advantage of surface functionalities that may be appropriately modified through mutation or bioconjugation. Herein we describe the design and application of hybrid VLPs for use as potent heparin antagonists, providing an alternative to the toxic heparin antidote protamine. A two-plasmid system was utilized to generate VLPs that contain both the wild-type coat protein and a second coat protein with either a C- or N-terminal cationic peptide extension (4-28 amino acids). Incorporation of the modified coat proteins varied from 8 to 31%, while activated partial thromboplastin time (APTT) assays revealed a range of the heparin antagonist activity. Notably, when examined on the basis of the quantity of peptide delivered due to the varied incorporation rates, it appeared that the VLPs largely followed a similar trend, with the quantity of peptide delivered more closely correlating with heparin antagonist activity. The particle with the highest incorporation rate and best antiheparin activity displayed the C-terminal peptide ARK <subscript>2</subscript> A <subscript>2</subscript> KA, which corresponds to the Cardin-Weintraub consensus sequence for binding to glycosaminoglycans. Analysis of this particle using heparin affinity chromatography with fraction collection revealed that particles eluting at higher salt concentration had a greater proportion of peptide incorporation. Preliminary dual polarization interferometry experiments further support a strong interaction between this particle and heparin.
- Subjects :
- Allolevivirus chemistry
Biological Assay methods
Drug Compounding methods
Drug Design
Humans
Partial Thromboplastin Time
Plasma drug effects
Capsid Proteins chemistry
Drug Carriers chemistry
Heparin Antagonists administration & dosage
Nanoparticles chemistry
Peptides administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 15
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 29902009
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.8b00135