A5062165641- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Advanced biosensing and bioanalysis techniques
- Bacteriophages and microbial interactions
- Advanced Biosensing Techniques and Applications
- Chemical Synthesis and Analysis
- Biosensors and Analytical Detection
- Innovative Microfluidic and Catalytic Techniques Innovation
- Insect Pest Control Strategies
- Phytochemistry and Biological Activities
- T-cell and B-cell Immunology
- Cholinesterase and Neurodegenerative Diseases
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Protease and Inhibitor Mechanisms
- Biochemical and Structural Characterization
- Allelopathy and phytotoxic interactions
- Peptidase Inhibition and Analysis
- Phytochemicals and Antioxidant Activities
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Natural product bioactivities and synthesis
- Alkaloids: synthesis and pharmacology
- Cell Adhesion Molecules Research
Amgen (Canada)
2021-2022
University of Alberta
2011-2021
Alberta Glycomics Centre
2012-2016
Indiana University – Purdue University Indianapolis
2016
Alberta Hospital Edmonton
2016
Stanford University
2013
Durban University of Technology
2010
University of Manitoba
2009-2010
University of Winnipeg
2009-2010
Manitoba Beekeepers' Association
2010
New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow rapidly screen optimize constructs containing multiple computationally designed miniprotein inhibitors SARS-CoV-2. We found broadest efficacy was achieved with homotrimeric version 75-residue angiotensin-converting enzyme (ACE2) mimic AHB2 (TRI2-2) geometrically match trimeric spike architecture....
Phage display empowered the development of proteins with new function and ligands for clinically relevant targets. In this report, we use next-generation sequencing to analyze phage-displayed libraries uncover a strong bias induced by amplification preferences phage in bacteria. This favors fast-growing sequences that collectively constitute <0.01% available diversity. Specifically, library 109 random 7-mer peptides (Ph.D.-7) includes few thousand grow quickly (the 'parasites'), which are...
Phage display is a powerful technology that enables the discovery of peptide ligands for many targets. Chemical modification phage libraries have allowed identification with properties not encountered in natural polypeptides. In this report, we demonstrated synthesis 2 × 10(8) genetically encoded glycopeptides from commercially available phage-displayed library (Ph.D.-7) two-step, one-pot reaction <1.5 h. Unlike previous reports, bypassed genetic engineering phage. The glycan moiety was...
Light-responsive ligands are useful tools in biochemistry and cell biology because the function of these can be spatially temporally controlled. Conventional design such relies on previously available data about structure both ligand receptor. In this paper, we describe de novo discovery light-responsive through screening a genetically encoded library. We ligated photoresponsive azobenzene core to random CX7C peptide library displayed coat protein M13 phage. A one-pot alkylation/reduction...
Abstract A simple method is described for the patterned deposition of Teflon on paper to create an integrated platform parallel organic synthesis and cell‐based assays. Solvent‐repelling barriers made Teflon‐impregnated confine solvents specific zones array allow 96 flow‐through syntheses paper. The confinement mixing significantly improves peptide yield simplifies automation this synthesis. 100 peptides ranging from 7 14 amino acids in length gave over 60 % purity majority (>95 per...
Agonism of members the tumor necrosis factor receptor superfamily (TNFRSF) with monoclonal antibodies is high therapeutic interest due to their role in immune regulation and cell proliferation. A major hurdle for pharmacologic activation this class requirement high-order clustering, a mechanism that imposes reliance vivo on Fc receptor-mediated crosslinking. This extrinsic dependence represents potential limitation virtually entire pipeline agonist TNFRSF antibody drugs, which none have thus...
Acetylcholinesterase (AChE) inhibition-directed phytochemical studies on the methanolic extract of Buxus natalensis, collected in South Africa, resulted isolation 12 compounds: O2-natafuranamine (1), O10-natafuranamine (2), cyclonataminol (3), 31-demethylbuxaminol A (4), buxaminol (5), buxafuranamide (6), buxalongifolamidine (7), buxamine (8), cyclobuxophylline K (9), C (10), methyl syringate (11), and p-coumaroylputrescine (12). Compounds 1−4 were new alkaloids, compound 5 was isolated for...
Escape variants of SARS-CoV-2 are threatening to prolong the COVID-19 pandemic. To address this challenge, we developed multivalent protein-based minibinders as potential prophylactic and therapeutic agents. Homotrimers single fusions three distinct were designed geometrically match spike (S) trimer architecture optimized by cell-free expression found exhibit virtually no measurable dissociation upon binding. Cryo-electron microscopy (cryoEM) showed that these trivalent engage all receptor...
The crude ethanolic extract of Nauclea latifolia yielded five known compounds, strictosamide (1), naucleamides A (2), naucleamide F (3), quinovic acid-3-O-β-rhamnosylpyranoside (4), and acid 3-O-β-fucosylpyranoside (5). Microbial reactions, using a whole cell culture Rhizopus circinans on compound three analogues, 10-hydroxystrictosamide (6), 10-4bT-glucosyloxyvincoside lactam (7) 16,17-dihydro-10-β-glucosyloxyvincoside (8). Compounds 1-8 were identified with the aid extensive NMR spectral...
In spite of the power phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied one member serpin superfamily. Here we describe human alpha-1 proteinase inhibitor (API) a T7 bacteriophage system. API M358R fused C-terminus capsid protein 10B was directly shown form denaturation-resistant complexes thrombin by electrophoresis and immunoblotting following exposure intact phages thrombin. We therefore developed biopanning...
Next-generation sequencing techniques empower selection of ligands from phage-display libraries because they can detect low abundant clones and quantify changes in the copy numbers without excessive rounds. Identification errors deep data is most critical step this process these have error rates >1%. Mechanisms that yield Illumina other been proposed, but no reports to date describe analysis phage libraries. Our paper focuses on 7-mer peptide sequenced by method. Low theoretical...
Abstract A simple method is described for the patterned deposition of Teflon on paper to create an integrated platform parallel organic synthesis and cell‐based assays. Solvent‐repelling barriers made Teflon‐impregnated confine solvents specific zones array allow 96 flow‐through syntheses paper. The confinement mixing significantly improves peptide yield simplifies automation this synthesis. 100 peptides ranging from 7 14 amino acids in length gave over 60 % purity majority (>95 per...
Significance Weak transient interactions are fundamental to immune responses, enabling avidity-driven triggers for pathogen neutralization and cellular regulation. In contrast obligate binding that can be directly investigated structurally, the low or transitory abundance of weak make them difficult identify characterize. This study leverages receptor agonism systems sensitive oligomerization investigate homotypic interfaces between antibody Fab regions. Our results show self-association...
In this report, we describe the methodology for 96 parallel organic syntheses of peptides on Teflon-patterned paper assisted by heating with an infra-red lamp.
The most robust strategy in antibody discovery is the use of immunized animals and ability to isolate immortalize immune B-cells hybridoma for further interrogation. However, capturing full repertoire an animal labor intensive, time consuming limited throughput. Therefore, techniques directly mine primary are great importance discovery. In current study, we present a method individual antigen-specific using CellCellector™ single-cell isolation platform from XenoMouse® (XM) with recombinant...
Abstract Many pharmaceutically-relevant cell surface receptors are functional only in the context of intact cells. Phage display, while being a powerful method for discovery ligands purified proteins often fails to identify diverse set on membrane mosaic. To understand this deficiency, we examined growth bias naïve phage display libraries and observed that it fundamentally changes selection outcomes: The presence growth-biased (parasite) clones library is detrimental cell-based panning such...