Abstract Noroviruses are a primary cause of gastroenteritis and foodborne illness with cases that affect millions people worldwide each year. Inexpensive tests for norovirus do not require sophisticated laboratory equipment important tools ensuring patients receive timely treatment containing outbreaks. Herein, we demonstrate low-cost colorimetric assay detects from clinical samples by combining paper-based cell-free transcription–translation systems, isothermal amplification virus...

A full understanding of the proteome will require ligands to all proteins encoded by genomes. While antibodies represent principle affinity reagents used bind proteins, their limitations have created a need for new large numbers proteins. Here we propose general concept obtain protein that avoids animal immunization and iterative selection steps. Central this process is idea small peptide libraries contain sequences independent regions on surface these can be combined synthetic scaffolds...

Noroviruses are a leading cause of foodborne illnesses worldwide. Although GII.4 strains have been responsible for most norovirus outbreaks, the assembled virus shell structures available in detail only single strain (GI.1). We present high-resolution (2.6- to 4.1-Å) cryoelectron microscopy (cryo-EM) GII.4, GII.2, GI.7, and GI.1 human outbreak virus-like particles (VLPs). VLPs thought exist single-sized assembly, our reveal polymorphism between within genogroups, with small, medium, large...

The cyclic heptapeptide microcystin toxins produced by a strain of Microcystis aeruginosa that has not been investigated previously were separated liquid chromatography and identified high-accuracy m/z measurements their [M + H]+ ions the fragment collision-activated dissociation ions. cyanobacteria B2666 was cultured in standard growth medium, released from cells, extracted aqueous phase, concentrated using procedures. microcystins reversed-phase microbore introduced directly into hybrid...

OPINION article Front. Microbiol., 25 December 2013Sec. Antimicrobials, Resistance and Chemotherapy Volume 4 - 2013 | https://doi.org/10.3389/fmicb.2013.00402

One proposed solution to the crisis of antimicrobial resistant (AMR) infections is development molecules that potentiate activity antibiotics for AMR bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Rather than develop broad spectrum compounds, we developed a peptide could narrow antibiotic, oxacillin. In this way, combination treatment narrowly target pathogen and limit impact on host flora. We peptide, ASU014, composed S. binding inhibitory conjugated branched...

Background There is a pressing need for high-affinity protein binding ligands all proteins in the human and other proteomes. Numerous groups are working to develop but most approaches using same strategy which large library of structured screened against target identify ligand target. While this methodology generates target, it generally an iterative process that can be difficult adapt generation numbers proteins. Methodology/Principal Findings We have developed class peptide-based ligands,...

The rise in antibiotic resistance has led to an increased research focus on discovery of new antibacterial candidates. While broad-spectrum antibiotics are widely pursued, there is evidence that arises part from the wide spread use these antibiotics. Our group developed a system produce protein affinity agents, called synbodies, which have high and specificity for their target. In this report, we describe adaptation candidates towards target bacterium. functions by screening bacteria against...

In combinatorial chemical approaches, optimizing the composition and arrangement of building blocks toward a particular function has been done using number methods, including high throughput molecular screening, evolution, computational prescreening. Here, different approach is considered that uses sparse measurements library molecules as input to machine learning algorithm which generates comprehensive, quantitative relationship between covalent structure can then be used predict any...

Immunodominant epitope discovery platforms play an important role in identifying novel biomarkers for effective immunotherapies and diagnostics. Methods to analyze the B-cell repertoire have been improved both experimentally computationally. We developed enhanced peptide microarray platform discover subsequently screen immunodominant epitopes. utilized SARS-Cov-2 IgG positive negative samples as a proof-of-concept demonstrate power of these microarrays. The method identified significantly...

Noroviruses are the most common cause of acute gastroenteritis in developed world. a diverse group nonenveloped RNA viruses that continuously evolving. This leads to rise immunologically distinct strains same genotype on frequent basis. diversity presents unique challenge for detection and tracking new strains, with continuous need norovirus affinity ligands. Our family bivalent synbody ligands using virus-like particle (VLP) from 2006 GII.4 Minerva strain norovirus. We produced more than 20...

Synbodies show promise as a new class of synthetic antibiotics. Here, we explore improvements in their activity and production through conjugation chemistry. Maleimide is widely used strategy due to its high yield, selectivity, low cost. We this conjugate two antibacterial peptides produce bivalent peptide, called synbody that has bactericidal against methicillin resistant Staphylococcus aureus (MRSA). The was prepared by partially d-amino acid substituted peptide bis-maleimide scaffold....

Background There is a significant need for affinity reagents with high target affinity/specificity that can be developed rapidly and inexpensively. Existing reagent development approaches, including protein mutagenesis, directed evolution, fragment-based design utilize large libraries and/or require structural information thereby adding time expense. Until now, no systematic approach to existed could produce nanomolar from small chemically synthesized peptide without the aid of information....

One approach to prepare protein binding ligands is join two low-affinity that bind different sites on the target create a high-affinity bivalent ligand. This typically requires some knowledge of ligand site and exquisite orientation in order achieve maximum affinity. Here, we explored limit affinity improvement possible with no priori peptide minimal effort spent linking lead peptides. We compared enhancement from peptides low for tumor necrosis factor-α (TNFA) improved versions these using...

The heterogeneous pathophysiology of traumatic brain injury (TBI) is a barrier to advancing diagnostics and therapeutics, including targeted drug delivery. We used unique discovery pipeline identify novel targeting motifs that recognize specific temporal phases TBI pathology. This combined in vivo biopanning with domain antibody (dAb) phage display, next-generation sequencing analysis, peptide synthesis. identified based on the complementarity-determining region 3 structure dAbs for acute (1...

There is an ongoing need for affinity agents emerging viruses and new strains of current human viruses. We therefore developed a robust modular system engineering high-affinity synbody ligands the influenza A/Puerto Rico/8/1934 H1N1 virus as model system. Whole-virus screening against peptide microarray was used to identify binding peptides. Candidate peptides were linked bis-maleimide scaffolds produce library candidate influenza-binding synbodies. From this library, synbody, ASU1060,...

Abstract Background It is widely hoped that personal cancer vaccines will extend the number of patients benefiting from checkpoint and other immunotherapies. However, it clear creating such be challenging. requires obtaining sequencing tumor DNA/RNA, predicting potentially immunogenic neoepitopes manufacturing a one-use vaccine. This process takes time considerable cost. Importantly, most mutations not produce an peptide many patient’s tumors do contain enough DNA to make We have discovered...

Past studies have shown that incubation of human serum samples on high density peptide arrays followed by measurement total antibody bound to each sequence allows detection and discrimination humoral immune responses a variety infectious diseases. This is true even though these consist peptides with near-random amino acid sequences were not designed mimic biological antigens. "immunosignature" approach, based statistical evaluation the binding pattern for sample but it ignores information...

Abstract Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed contain outbreak. We present a simple concept rapid development of new antimicrobials. The goal was produce in as little one week thousands doses an intervention pathogen. tested feasibility system based on antimicrobial synbodies. involves creating array 100 peptides have been selected broad capability bind and/or kill viruses and bacteria. are...

We demonstrate a platform to screen virus pseudotyped with Ebola glycoprotein (GP) against library of peptides that contain non-natural amino acids develop GP affinity ligands. This system could be used for rapid development peptide-based antivirals other emerging or neglected tropical infectious diseases.

It has been observed that under MeV-ion bombardment of a polymer, such as polycarbonate (PC) or polyvinylidene fluoride (PVDF), large quantities carbon clusters $({\mathrm{C}}_{n}^{\ensuremath{-}}$ and ${\mathrm{C}}_{n}{\mathrm{H}}^{\mathrm{\ensuremath{-}}})$ are generated. However, when PC PVDF is bombarded with keV atomic ions, very few carbon-cluster ions produced. This different behavior was attributed to the sputtering/desorption mechanisms for keV- impacts. Low-energy deposit their...