A5062952482- RNA Interference and Gene Delivery
- Supramolecular Self-Assembly in Materials
- Advanced biosensing and bioanalysis techniques
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Polydiacetylene-based materials and applications
- Biosensors and Analytical Detection
- Proteins in Food Systems
- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Luminescence and Fluorescent Materials
- Infant Nutrition and Health
- Gold and Silver Nanoparticles Synthesis and Applications
- Peptidase Inhibition and Analysis
- Polymer Surface Interaction Studies
- Escherichia coli research studies
- Endoplasmic Reticulum Stress and Disease
- Molecular Sensors and Ion Detection
- Antibiotics Pharmacokinetics and Efficacy
- Nanocluster Synthesis and Applications
- Bacterial Genetics and Biotechnology
- Laser-Ablation Synthesis of Nanoparticles
- Cell Adhesion Molecules Research
Nanyang Technological University
2017-2024
Linköping University
2013-2017
Kansas State University
2009-2016
Peptide coacervates self-assembling via liquid-liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non-cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross membranes remain unknown. Here, using multimodal imaging, data analytics, biochemical inhibition assays, identify key steps enter cell. find that uptake follows a...
Peptide-based packaging systems show great potential as safer drug delivery systems. They overcome problems associated with lipid-based or viral systems, vis-a-vis stability, specificity, inflammation, antigenicity, and tune-ability. Here, we describe a set of 15 & 23-residue branched, amphiphilic peptides that mimic phosphoglycerides in molecular architecture. These undergo supramolecular self-assembly form solvent-filled, bilayer delimited spheres 50–200 nm diameters confirmed by TEM, STEM...
Peptide-based liquid droplets (coacervates) produced by spontaneous liquid-liquid phase separation (LLPS), have emerged as a promising class of drug delivery systems due to their high entrapping efficiency and the simplicity formulation. However, detailed mechanisms governing interaction with cell membranes cellular uptake remain poorly understood. In this study, we investigated interactions peptide coacervates composed HB pep —peptide derived from histidine-rich beak proteins (HBPs)...
Identifying peptide substrates that are efficiently cleaved by proteases gives insights into substrate recognition and specificity, guides development of inhibitors, improves assay sensitivity. Peptide arrays SAMDI mass spectrometry were used to identify a tetrapeptide exhibiting high activity for the bacterial outer-membrane protease (OmpT). Analysis preferred residues at cleavage site (P1, P1') nearest-neighbor positions (P2, P2') their positional interdependence revealed FRRV as optimal...
Rationally designed biomolecular condensates have found applications primarily as drug-delivery systems, thanks to their ability self-assemble under physico-chemical triggers (such temperature, pH, or ionic strength) and concomitantly trap client molecules with exceptionally high efficiency (>99%). However, potential in (bio)sensing remains unexplored. Here, we describe a simple rapid assay detect E. coli by combining phase-separating peptide containing protease recognition site, within...
Over the past decade, peptides have emerged as a new family of potential carriers in gene therapy. Peptides are easy to synthesize and quite stable. Additionally, sequences shared by host proteome not expected be immunogenic or trigger inflammatory responses, which commonly observed with viral approaches. We recently reported on class branched amphiphilic peptide capsules (BAPCs) that self-assemble into extremely stable nanospheres. These capable retaining delivering alpha-emitting...
ABSTRACT This study explores the dynamic and hierarchical structural organization of peptide coacervate microdroplets at meso-to atomic-scale resolution using a combination Transferred Nuclear Overhauser Effect Spectroscopy (TrNOESY), Small Angle Neutron Scattering (SANS), confocal microscopy. Dynamic interactions driving self-association clusters are revealed, highlighting critical roles interacting residues. These phase-separating model peptides form small oligomers low pH, which aggregate...
In a recent article (Gudlur et al. PLOS ONE, 2012, 7 (9) e45374), we described the special properties of mixed branched peptide assembly in which equimolar bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK self-associate to form bilayer delimited capsules capable trapping solutes. These polycationic vesicle-like are readily taken up by epithelial cells culture, escape or evade endocytic pathway, accumulate perinuclear region where they persist without any apparent degradation. this report, examine...
Abstract The synthesis and characterization of a new protein–polymer conjugate composed β lactoglobulin A (βLG A) poly(ethylene glycol) PEG is described. βLG was selectively modified to self‐assemble by super‐charging via amination or succinylation followed conjugation with PEG. An equimolar mixture the oppositely charged conjugates into spherical capsules 80–100 nm in diameter. self‐assembly proceeds taking simultaneous advantage amphiphilicity polyelectrolyte nature conjugate. These...
Abstract Identifying peptide substrates that are efficiently cleaved by proteases gives insights into substrate recognition and specificity, guides development of inhibitors, improves assay sensitivity. Peptide arrays SAMDI mass spectrometry were used to identify a tetrapeptide exhibiting high activity for the bacterial outer‐membrane protease (OmpT). Analysis preferred residues at cleavage site (P1, P1′) nearest‐neighbor positions (P2, P2′) their positional interdependence revealed FRRV as...
Abstract Coacervates are dense microdroplets formed by liquid-liquid phase separation (LLPS) of macromolecules that have gained increasing attention as drug delivery vehicles. Recently, we reported a new intracellular system based on self-coacervating histidine (His)-rich beak peptides (HB pep and HB -SP) inspired proteins the Humboldt squid. These peptide combine excellent encapsulation efficiency therapeutics with high transfection rate low cytotoxicity. However, mechanism which they cross...
Outer membrane protease (OmpT) is a 33.5 kDa aspartyl that cleaves at dibasic sites and thought to function as defense mechanism for E. coli against cationic antimicrobial peptides secreted by the host immune system. Despite carrying three in its own sequence, there no report of OmpT autoproteolysis vivo. However, recombinant expressed vitro inclusion bodies has been reported undergo during refolding step, thus resulting an inactive protease. In this study, we monitor compare levels folded...
E. coli and Salmonella are two of the most common bacterial pathogens involved in foodborne waterborne related deaths. Hence, it is critical to develop rapid sensitive detection strategies for near-outbreak applications. Reported a simple specific assay detect as low 1 CFU mL-1 water within 6 hours by targeting bacteria's surface protease activity. The relies on polythiophene acetic acid (PTAA) an optical reporter short unlabeled peptide (LL37FRRV ) previously optimized substrate OmpT,...
Shape-directing agents that promote anisotropic growth are frequently employed in the synthesis of gold nanorods (GNRs), a typical example which is surfactant cetyltrimethylammonium bromide (CTAB). Owing to their cytotoxicity, surfactant-passivated GNRs have little use biological applications unless made biocompatible via additional downstream processing. Reported herein first instance liposome-directed synthesized absence surfactants. The as-synthesized phospholipid-passivated readily...
Recent improvements in methods for rapid detection of microbial contamination food and water samples have aided the development on-site point-of-care testing. Early detection, made possible via testing, can help limit spread waterborne illnesses. Recently, we reported a novel fluorescence-based Omptin-Polythiophene assay (the assay) to detect Escherichia coli contaminated samples. The targets OmpT─an E. outer membrane protease─and exploits protease's ability cleave at dibasic sites within...
Abstract E. coli and Salmonella are two of the most common bacterial pathogens involved in foodborne waterborne related deaths. Hence, it is critical to develop rapid sensitive detection strategies for near‐outbreak applications. Reported a simple specific assay detect as low 1 CFU mL −1 water within 6 hours by targeting bacteria's surface protease activity. The relies on polythiophene acetic acid (PTAA) an optical reporter short unlabeled peptide (LL37 FRRV ) previously optimized substrate...
Abstract The synthesis and characterization of a new protein–polymer conjugate composed β lactoglobulin A (βLG A) poly(ethylene glycol) PEG is described. βLG was selectively modified to self‐assemble by super‐charging via amination or succinylation followed conjugation with PEG. An equimolar mixture the oppositely charged conjugates into spherical capsules 80–100 nm in diameter. self‐assembly proceeds taking simultaneous advantage amphiphilicity polyelectrolyte nature conjugate. These...