A5038178757- Nicotinic Acetylcholine Receptors Study
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- Alzheimer's disease research and treatments
- Synthesis and Biological Evaluation
- Neurotransmitter Receptor Influence on Behavior
- Biochemical and Structural Characterization
- Peptidase Inhibition and Analysis
- Supramolecular Self-Assembly in Materials
- Antimicrobial Peptides and Activities
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Ion channel regulation and function
- RNA Interference and Gene Delivery
- Cholesterol and Lipid Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Machine Learning in Bioinformatics
- Organoselenium and organotellurium chemistry
- Organic Chemistry Cycloaddition Reactions
- Neurobiology and Insect Physiology Research
- Drug Transport and Resistance Mechanisms
- Chemical Reactions and Mechanisms
- RNA Research and Splicing
- ATP Synthase and ATPases Research
The University of Queensland
2003-2025
Fred Hutch Cancer Center
2018-2020
University of Washington
2013-2016
University of Geneva
2003
Secs for your folding problems: Selenocysteine (Sec) residues were used to drive the of conotoxin MrVIB, a previously "unfoldable" miniprotein with therapeutic potential (see picture). This simple strategy should generally facilitate peptides and proteins multiple disulfide bonds. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: The...
Previous studies suggest that the toxic soluble-oligomeric form of different amyloid proteins share a common backbone conformation, but amorphous nature this oligomer prevents its structural characterization by experiment. Based on molecular dynamics simulations we proposed intermediates adopt common, nonstandard secondary structure, called α-sheet. Here report experimental peptides designed to be complementary α-sheet conformation observed in simulations. We demonstrate inhibition...
The trefoil factor family (TFF) comprises three secretory peptides (TFF1, TFF2, TFF3) that regulate diverse physiological processes to maintain gastrointestinal mucosal integrity and homeostasis. TFF domain is stabilized by six conserved cysteine residues forming intramolecular disulfide bonds. In this work, we investigated human TFF1 stability against increasing concentrations of the reducing agent tris(2-carboxyethyl)phosphine (TCEP). Experiments revealed high resistance bonds within...
A scorpion-derived peptide-steroid conjugate accumulates in cartilage and reverses inflammation a rat model of arthritis without steroid toxicity.
d-amino acids are useful building blocks for de novo peptide design and they play a role in aging-related diseases associated with gradual protein racemization. For amino achiral side chains, one should be able to presume that the conformational propensities of l- reflection another due straightforward geometric inversion at Cα atom. However, this presumption does not account directionality backbone dipole inverted have never been definitively confirmed context. Furthermore, there is little...
The impenetrability of the blood-brain barrier (BBB) to most conventional drugs impedes treatment central nervous system (CNS) disorders. Interventions for diseases like brain cancer, neurodegeneration, or age-associated inflammatory processes require varied approaches CNS drug delivery. Cystine-dense peptides (CDPs) have drawn recent interest as drug-delivery vehicles. Found throughout phylogenetic tree, often in drug-like roles, their size, stability, and protein interaction capabilities...
The effects of the native α-conotoxin PnIA, its synthetic derivative [A10L]PnIA and alanine scan derivatives were investigated on chick wild type α7 α7-L247T mutant nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes. PnIA inhibited (ACh)-activated currents at wtα7 with IC50 values 349 168 nm, respectively. Rates onset inhibition similar for [A10L]PnIA; however, rate recovery was slower [A10L]PnIA, indicating that increased potency is conveyed by dissociation from...
The trpzip peptides are small, monomeric, and extremely stable β-hairpins that have become valuable tools for studying protein folding. Here, we show trpzip-3 inhibits aggregation in two very different amyloid systems: transthyretin Aβ(1-42). Interestingly, Trp → Leu mutations renders the peptide ineffective against transthyretin, but Aβ inhibition remains. Computational docking was used to predict interactions between suggesting occurs via binding outer region of thyroxine-binding site,...
Eine Lösung für Faltungsprobleme: Selenocystein(Sec)-Reste wurden genutzt, um die Faltung von Conotoxin MrVIB, einem vormals "unfaltbaren" Miniprotein mit therapeutischem Potenzial, zu induzieren (siehe Bild). Diese Strategie einfache Peptiden und Proteinen mehreren Disulfidbindungen dürfte allgemein anwendbar sein.
Conotoxins, a class of marine peptides rich in disulfide bonds, contain many the structural elements present larger proteins, such as α-helices and β-turns. In addition, these natural products are remarkably stable exhibit exceptional receptor selectivity. These properties make them ideal candidates for drug development.
Grafting different regions of related peptides together to form a single protein chimera is valuable tool in rapidly elucidating activity or selectivity and proteins. To conveniently evaluate the contributions N- C-terminal segments ω-conotoxins CVID MVIIC activity, we employed native chemical ligation CVID-MVIIC design. Assembly these peptide via method improved overall yield coupling efficiency, with no difficult sequences encountered contrast traditional full-length chain assembly CVID....
The standard p-MBHA resin used during Boc-chemistry synthesis of peptides carrying C-terminal carboxamides is compromised by batch-to-batch variations in its performance. This can cause artificially 'difficult' couplings peptide chain assembly, which may ultimately lead to failed syntheses given the inability achieve acceptable coupling yields. To overcome these problems, we have developed a new approach grafting functionalized benzhydrylamine linker onto well-characterized and...
Developments in imaging have improved cancer diagnosis, but identification of malignant cells during surgical resection remains a challenge. The aim this study was to investigate the pacifastin family peptides for novel activity targeting tumor and delivery either or therapeutic agents.Variants were generated, chemically modified tested human xenografts.A tumor-homing peptide-dye conjugate (THP1) accumulated tumors vivo internalized into cells. Examination related revealed residues critical...