A5003095181- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Click Chemistry and Applications
- Biochemical and Structural Characterization
- Antimicrobial Peptides and Activities
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Polydiacetylene-based materials and applications
- Protein purification and stability
- Crystallography and molecular interactions
- X-ray Diffraction in Crystallography
- Immune Response and Inflammation
- Crystallization and Solubility Studies
- Enzyme Production and Characterization
- Metal complexes synthesis and properties
- Chemical Synthesis and Reactions
- DNA Repair Mechanisms
- Phytochemical compounds biological activities
- Food Allergy and Anaphylaxis Research
- Asymmetric Hydrogenation and Catalysis
- Organophosphorus compounds synthesis
- Sulfur-Based Synthesis Techniques
- Cancer-related Molecular Pathways
- Inorganic and Organometallic Chemistry
University College London
2011-2023
The London College
2023
Transnational Press London
2015-2021
Danish Cancer Society
2012
University of Copenhagen
2012
Novo Nordisk Foundation
2012
University of Zurich
2012
Osaka University
2012
University of Edinburgh
2001-2010
Medical Research Council
2010
Respiratory syncytial virus is a leading cause of lower respiratory tract illness among infants, the elderly and immunocompromised individuals. Currently, there no effective vaccine or disease modifying treatment available novel interventions are urgently required. Cathelicidins cationic host defence peptides expressed in inflamed lung, with key roles innate against infection. We demonstrate that human cathelicidin LL-37 has antiviral activity RSV vitro, retained by truncated central peptide...
Eosinophils have previously been shown to accumulate around the tissue invasive (L3) stage of sheep gastrointestinal parasites in vivo. In this study, eosinophils obtained from mammary washes sheep, were immobilize and kill H. contortus larvae vitro presence antibody specific against a defined L3 surface antigen. primed by repeated infusion more effective than after single parasite extract Fasciola hepatica infected ewes suggesting former activated The level larval immobilization was...
The decomposition of ethylenediaminetetraacetic acid (EDTA) in water solution at 200 and 260 °C, nitrilotriacetic (NTA) 293 nitrilotrimethylenephosphonic (NTPO) °C was studied by n.m.r. as a function time pH 9.5 rates products were determined. primary (fast) reaction EDTA involves the hydrolytic cleavage ethylenic C—N bond to produce relatively stable pair: N-(2-hydroxyethyl)iminodiacetic iminodiacetic acid. NTA does not cleave below but decomposes about 290 above through stepwise...
Peptides and proteins fragment sequence-specifically in the presence of 3-mercaptopropionic acid to afford thioesters which can be used native chemical ligation reactions.
Peptide and protein thioesters are playing an increasingly prominent role in the chemical toolbox for assembly modification through Native Chemical Ligation (NCL). In this Emerging Area we highlight recent developments a somewhat surprising route to thioesters: selective disruption of amides, more stable carboxylic acid derivatives.
Rapid, facile routes to the TFA-cleavable 4,5,6-trimethoxy-2-mercaptobenzyl and 1-(2,4-dimethoxyphenyl)-2-mercaptoethyl classes of auxiliaries for cysteine-free native chemical ligation are described. Rapid synthesis, coupled with mild cleavage conditions will undoubtedly broaden utility such auxiliaries, particularly where chemically fragile peptide modifications as glycosylation present.
Put the two together: Physiologically relevant glycoproteins containing saccharides at predetermined sites, such as GlyCAM-1, can be generated from small synthetic and bacterially derived fragments by using expressed protein ligation methodology. This technique was used for synthesis of three semisynthetic GlyCAM-1 variants 1–3 (see scheme). Supporting information this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z52673_s.pdf or author. Please note: The...
Highly expressive: Cell proliferation was observed with concentrations of an erythropoietin (EPO) analogue above 50 pg mL−1. The EPO has two human complex-type sialyloligosaccharides (see picture) and formed by the combined use chemical synthesis protein expression in E. coli. Both 24- 30-positions are glycosylated, but do not interfere binding to a receptor. Detailed facts importance specialist readers published as "Supporting Information". Such documents peer-reviewed, copy-edited or...
We describe here a new ion mobility capable mass spectrometer which comprises drift cell for separation and quadrapole time of flight analysis—the MoQTOF. A commercial QToF instrument (Micromass UK Ltd., Manchester, UK) has been modified by the inclusion an additional chamber containing ancillary optics. The is 5.1 cm long made from copper block mounted top hat flange in situated post source optics prior to quadapole analyzer. Details this are provided along with information about how it can...
Tagging the terminus: N→S acyl transfer in native peptides and proteins can be reliably intercepted with hydrazine. The method allows selective labeling ligation, without recourse to use of protein-splicing elements. NCL=native chemical ligation. In 1998, Ramage group demonstrated that a C-terminal hydrazide synthetic peptide could, following diazotization corresponding azide, transformed into usefully functionalized peptides, including thioesters.1 A drawback was certain amino acid residues...
The leucine zipper interaction between MAX and c-MYC has been studied using mass spectrometry drift time ion mobility (DT IM-MS) in addition to circular dichroism spectroscopy. Peptides comprising the sequence with (c-MYC-Zip residues 402-434) without a postulated small-molecule binding region (c-MYC-ZipΔDT 406-434) have synthesized, along corresponding (MAX-Zip 74-102). c-MYC-Zip:MAX-Zip complexes are observed both absence presence of reported inhibitor 10058-F4 for forms c-MYC-Zip. DT...
Mdc1 is a large modular phosphoprotein scaffold that maintains signaling and repair complexes at double-stranded DNA break sites. anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with the tail γH2AX following damage, but role N-terminal forkhead-associated (FHA) remains unclear. We show major binding target FHA previously unidentified damage ATM-dependent phosphorylation site near N-terminus itself. Binding this motif stabilizes weak self-association...
Peptide thioesters readily prepared through N→S acyl transfer of a specific C-terminal motif provide access to biologically active mini-proteins using native chemical ligation.
Abstract Peptide thioester synthesis by N→S acyl transfer is being intensively explored many research groups the world over. Reasons for this likely include often straightforward method of precursor assembly using Fmoc‐based chemistry and fundamentally interesting migration process. In review we introduce recent advances in exciting area discuss, more detail, our own efforts towards peptide thioesters through native sequences. We have found that several can be readily prepared and, what’s...
Tissue kallikreins (KLKs), in particular KLK5, 7 and 14 are the major serine proteases skin responsible for shedding activation of inflammatory cell signaling. In normal skin, their activities controlled by an endogenous protein protease inhibitor encoded SPINK5 gene. Loss-of-function mutations leads to enhanced kallikrein cause disease Netherton Syndrome (NS). We have been developing inhibitors based on Sunflower Trypsin Inhibitor 1 (SFTI-1) scaffold, a amino acids head-to-tail bicyclic...
Sugars and simplified oligosaccharide "mimics" can be joined with protein fragments at pre-defined sites using reliable chemical reactions such as thiol alkylation Cu(I) catalysed azide/acetylene ligation (click chemistry). These have the potential to assembled into neoglycoprotein therapeutics native ligation.
Latent thioesters: Reverse native chemical ligation followed by intramolecular trans-thioesterification and acyl transfer can rearrange linear peptides into biologically active cyclic products. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted the authors. Please note: The publisher is responsible for content functionality any supporting information supplied...
EPO-Doping: Bei Konzentrationen eines Erythropoietin(EPO)-Analogons über 50 pg mL−1 wurde Zellproliferation beobachtet. Das EPO-Analogon, das zwei humane Sialyloligosaccharide enthält (siehe Bild), mithilfe einer Kombination aus chemischer Synthese und Proteinexpression in E. coli erhalten. Die beiden stören nicht bei der Bindung des EPO-Analogons an einen Rezeptor. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but...
Peptide thioesters are important tools for the total synthesis of proteins using native chemical ligation (NCL). Preparation glycopeptide thioesters, that enable assembly homogeneously glycosylated proteins, is complicated by perceived fragile nature sugar moiety. Herein, we demonstrate compatibility thioester formation via N→S acyl transfer with N-glycopeptides and report observations will aid in their preparation.
Sunflower Trypsin Inhibitor (SFTI-1) analogues have been prepared from simple linear precursors produced either by chemical synthesis or following purification Escherichia coli. We shown, for the first time that these SFTI-1 derived peptide sequences can be converted to circular peptides via selective consecutive acyl transfer reactions, and products synthetic bacterial origin are identical. Preliminary analysis of semi-synthetic confirmed SFTI-I10H as an inhibitor Kallikrein-5 (KLK5)...