A5006223544- Chemical Synthesis and Analysis
- Supramolecular Self-Assembly in Materials
- Alzheimer's disease research and treatments
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Click Chemistry and Applications
- Protein Structure and Dynamics
- Toxin Mechanisms and Immunotoxins
- Antimicrobial Peptides and Activities
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Microbial Inactivation Methods
- Radiopharmaceutical Chemistry and Applications
- RNA Interference and Gene Delivery
- Bacillus and Francisella bacterial research
- Boron Compounds in Chemistry
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Catalytic Cross-Coupling Reactions
- Enzyme Catalysis and Immobilization
- Bladder and Urothelial Cancer Treatments
- Machine Learning in Bioinformatics
- Orthopedic Infections and Treatments
- CRISPR and Genetic Engineering
- Viral Infections and Outbreaks Research
University of South Carolina
2023-2025
University of California, Irvine
2016-2024
Massachusetts Institute of Technology
2019-2024
University of South Carolina Sumter
2023
University of California System
2016
Irvine Valley College
2016
Purdue University West Lafayette
2012
Carboranes represent a class of compounds with increasing therapeutic potential. However, few general approaches to readily embed carboranes into small molecules, peptides, and proteins are available. We report strategy based on palladium-mediated C–X (X = C, S, N) bond formation for the installation carborane-containing moieties onto molecules peptides. demonstrate ability Pd-based reagents appropriate ligands overcome high hydrophobicity carborane group enable chemoselective conjugation...
Interferon (IFN)-γ is a central regulator of cell-mediated immunity in human health and disease, but reduced expression the target receptors impairs signaling activity leads to immunotherapy resistance. Although intracellular IFN-γ restores downstream functions, we lack tools activate IFNG gene instead cell surface receptors. This paper introduces design characterization an artificial transcription factor (ATF) protein that recognizes with six zinc finger domains, which are dovetailed VP64...
This paper introduces a robust pipeline for preparing and studying synthetic fold-switching proteins using automated flow protein synthesis. Fold-switching are an expanding class of that remarkably switch from one stable fold to another in response subtle changes the sequence or chemical environment, without populating unfolded aggregated states. The polymorphism these permits important regulatory functions across biological processes diseases, but also hinders their preparation...
Precise control over the dosage of Cas9-based technologies is essential because off-target effects, mosaicism, chromosomal aberrations, immunogenicity, and genotoxicity can arise with prolonged Cas9 activity. Type II anti-CRISPR proteins (Acrs) inhibit but are generally impermeable to cell membrane due their size (6–54 kDa) anionic charge. Moreover, existing Acr delivery methods long-lived operate within hours ( e . g ., viral non-viral vectors) or not applicable in vivo nucleofection),...
In Alzheimer's disease, aggregation of the β-amyloid peptide (Aβ) results in formation oligomers and fibrils that are associated with neurodegeneration. Aggregation Aβ occurs through interactions between different regions peptide. This paper accompanying constitute a two-part investigation two key Aβ: central region C-terminal region. These promote adopt β-sheet structure fibrils, may also do so oligomers. this paper, we study assembly macrocyclic peptides contain residues 17-23 (LVFFAED)...
Amyloid-β (Aβ) forms heterogeneous oligomers, which are implicated in the pathogenesis of Alzheimer's disease (AD). Many Aβ oligomers consist β-hairpin building blocks─Aβ peptides conformations. β-Hairpins can adopt a variety alignments, but role that alignment plays formation and heterogeneity is poorly understood. To explore effect on oligomerization peptides, we designed studied two model with different alignments. Peptides Aβm
Abstract High-throughput genome sequencing and computation have enabled rapid identification of targets for personalized medicine, including cancer vaccines. Synthetic peptides are an established mode vaccine delivery, but generating the each patient in a affordable fashion remains difficult. peptide synthesis technology is therefore urgently needed patient-specific vaccines to succeed clinic. Previously, we developed automated flow that greatly accelerates production synthetic peptides....
In this paper, we investigate the coassembly of peptides derived from central and C-terminal regions β-amyloid peptide (Aβ). preceding J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b06000 , established that containing residues 17-23 (LVFFAED) region Aβ 30-36 (AIIGLMV) assemble to form homotetramers consisting two hydrogen-bonded dimers. Here, mix these tetramer-forming determine how they coassemble. Incorporation a single 15N isotopic label into each provides spectroscopic probe with which...
Bladder cancer is the sixth most common in United States, and it exhibits an alarming 70% recurrence rate. Thus, development of more efficient antibladder approaches a high priority. Accordingly, this work provides basis for transformative anticancer strategy that takes advantage unique characteristics bladder. Unlike mucin-shielded normal bladder cells, cells are exposed to lumen overexpress EGFR. Therefore, we used EGF-conjugated anthrax toxin after targeting EGFR was internalized...
The synthesis of palladium oxidative addition complexes derived from unprotected peptides is described. Incorporation 4-halophenylalanine into a peptide during solid phase allows for subsequent at this position upon treatment with precursor and suitable ligand. resulting palladium-peptide are solid, storable, water-soluble, easily purified via high-performance liquid chromatography. These react thiols in aqueous buffer, offering an efficient method bioconjugation. Using strategy, can be...
The nontoxic, anthrax protective antigen/lethal factor N-terminal domain (PA/LF
Molecular vaccines comprising antigen peptides and inflammatory cues make up a class of therapeutics that promote immunity against cancer pathogenic diseases but often exhibit limited efficacy. Here, we engineered an peptide delivery system to enhance vaccine efficacy by targeting dendritic cells mediating cytosolic delivery. The consists the nontoxic anthrax protein, protective (PA), single-chain variable fragment (scFv) recognizes XCR1 receptor on (DCs). Combining these proteins enabled...
This paper describes the synthesis, solution-phase biophysical studies, and X-ray crystallographic structures of hexamers formed by macrocyclic β-hairpin peptides derived from central C-terminal regions Aβ, which bear "tails" N-terminus Aβ. Soluble oligomers β-amyloid peptide, are thought to be synaptotoxic species responsible for neurodegeneration in Alzheimer's disease. Over last 20 years, evidence has accumulated that implicates Aβ as a region may initiate formation damaging oligomeric...
X-ray crystallography reveals that a macrocyclic peptide derived from transthyretin (TTR) assembles to form square channels.
Antisense oligonucleotide therapies are important cancer treatments, which can suppress genes in cells that critical for cell survival. SF3B1 has recently emerged as a promising gene target encodes key splicing factor the SF3B protein complex. Over 10% of cancers have lost one or more copies gene, rendering these vulnerable after further suppression. is just example CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) but over 120 additional candidate known....
Antigen processing is critical for therapeutic vaccines to generate epitopes priming cytotoxic T cell responses against cancer and pathogens, but insufficient often limits the quantity of released. We address this challenge using machine learning ascribe a proteasomal degradation score epitope sequences. Epitopes with varying scores were translocated into cells nontoxic anthrax proteins. low show pronounced immunogenicity due antigen processing, high limited immunogenicity. This work sheds...
Aggregation of the islet amyloid polypeptide (IAPP) to form fibrils and oligomers is important in progression type 2 diabetes. This article describes X-ray crystallographic solution-state NMR studies peptides derived from residues 11-17 IAPP that assemble tetramers. Incorporation (RLANFLV) into a macrocyclic β-sheet peptide results monomeric does not self-assemble oligomers. Mutation Arg
Therapeutic immunotoxins composed of antibodies and bacterial toxins provide potent activity against malignant cells, but joining them with a defined covalent bond while maintaining the desired function is challenging. Here, we develop novel by dovetailing full-length immunoglobulin G (IgG) nontoxic anthrax proteins, in which C terminus IgG heavy chain connected to side toxin protective antigen. This strategy enabled efficient conjugation antigen variants trastuzumab (Tmab) cetuximab (Cmab)...
Pd-catalyzed cross-coupling giving aryl-aryl, alkenyl-aryl, aryl-alkenyl, alkynyl-aryl, and alkynyl-alkenyl products exhibited ultra-high turnover numbers (TONs) of 0.7×10 7 ~0.69×10 9 by using organozincs generated in situ treatment the corresponding organolithiums with dry ZnBr 2 .Additionally, hydrozirconation-Pd-catalyzed tandem processes via 1-alkynes i Bu AlH-ZrCp Cl followed selective (≥98%) alkenyl-alkenyl coupling either (E)-or (Z)-ethyl 3-bromoacrylate high TONs 0.9×10 5 ~0.81×10...
ADVERTISEMENT RETURN TO ISSUEPREVViewpointNEXTTransmembrane Proteins: Amyloids Hidden in Plain Sight?Nicholas L. Truex and James S. Nowick*View Author Information Department of Chemistry, University California, Irvine, California 92697-2025, United States*E-mail: [email protected]. Phone: (949) 824-6091.Cite this: Biochemistry 2017, 56, 36, 4735–4736Publication Date (Web):August 30, 2017Publication History Received8 August 2017Published online30 inissue 12 September...
Abstract Antigen processing is critical for producing epitope peptides that are presented by HLA molecules T cell recognition. Therapeutic vaccines aim to harness these epitopes priming cytotoxic responses against cancer and pathogens, but insufficient often reduces vaccine efficacy through limiting the quantity of released. Here, we set out improve antigen harnessing protein degradation signals called degrons from ubiquitin-proteasome system. We used machine learning generate a...