A5056670044- Chemical Synthesis and Analysis
- Tissue Engineering and Regenerative Medicine
- Venomous Animal Envenomation and Studies
- Electrospun Nanofibers in Biomedical Applications
- Lipid Membrane Structure and Behavior
- Leech Biology and Applications
- Pluripotent Stem Cells Research
- Viral-associated cancers and disorders
- Neuroscience of respiration and sleep
- Congenital heart defects research
- Healthcare and Venom Research
- Neuropeptides and Animal Physiology
- Neonatal Respiratory Health Research
- Inhalation and Respiratory Drug Delivery
- Lymphoma Diagnosis and Treatment
- Cardiomyopathy and Myosin Studies
- Heparin-Induced Thrombocytopenia and Thrombosis
- Peptidase Inhibition and Analysis
- Viral Infections and Immunology Research
- Multiple Myeloma Research and Treatments
- Histiocytic Disorders and Treatments
- Cell Adhesion Molecules Research
- Synthetic Organic Chemistry Methods
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
Imperial College London
2018-2023
Imperial Valley College
2019
Hammersmith Hospital
2017-2019
University of Birmingham
2008-2010
The Honourable Society of Lincoln's Inn
2010
Cancer Research UK
2008
Monsanto (United States)
1999
Abstract Background The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in all EBV-associated tumours, including undifferentiated nasopharyngeal carcinoma (NPC), where it indispensable for viral replication, genome maintenance and gene expression. EBNA1's transcription factor-like functions also extend to influencing the expression of cellular genes involved pathways commonly dysregulated during oncogenesis, elevation AP-1 activity NPC cell lines resulting enhancement...
Hirudin, isolated from the European leech Hirudo medicinalis, is a potent inhibitor of thrombin, forming an almost irreversible thrombin-hirudin complex. Previously, we have shown that carboxyl terminus hirudin (residues 45-65) inhibits clotting activity and without binding to catalytic site thrombin. In present study, series peptides corresponding this carboxyl-terminal region been synthesized, their anticoagulant properties thrombin were examined. Binding was assessed by ability displace...
The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in all virus-associated tumours, including nasopharyngeal carcinoma (NPC), where it plays an essential role EBV genome maintenance, replication and transcription. Previous studies suggest that may have additional effects relevant to oncogenesis, enhancement of cell survival, raising the possibility influence cellular gene expression. We recently demonstrated by expression microarray profiling NPC model influences a range genes,...
Hypertrophic cardiomyopathy (HCM) is a primary disorder of contractility in heart muscle. To gain mechanistic insight and guide pharmacological rescue, this study models HCM using isogenic pairs human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the E99K-ACTC1 cardiac actin mutation. In both 3D engineered tissues 2D monolayers, arrhythmogenesis was evident all hiPSC-CMs. Aberrant phenotypes were most common hiPSC-CMs produced from heterozygote father....
Engineered heart tissue (EHT) strategies, by combining cells within a hydrogel matrix, may be novel therapy for failure. EHTs restore cardiac function in rodent injury models, but more data are needed clinically relevant settings. Accordingly, an upscaled EHT patch (2.5 cm × 1.5 mm) consisting of up to 20 million human induced pluripotent stem cell–derived cardiomyocytes (hPSC-CMs) embedded fibrin-based was developed. A rabbit myocardial infarction model then established test feasibility and...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMinimal peptide length for interaction of amphipathic .alpha.-helical peptides with phosphatidylcholine liposomesLarry R. McLean, Karen A. Hagaman, Thomas J. Owen, and John L. KrstenanskyCite this: Biochemistry 1991, 30, 1, 31–37Publication Date (Print):January 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://doi.org/10.1021/bi00215a005RIGHTS & PERMISSIONSArticle Views324Altmetric-Citations67LEARN ABOUT...
Porcine neuropeptide Y (pNPY) has been proposed to form an intramolecularly stabilized structure characterized by N- and C-terminal helical regions arranged antiparallel due a central turn region. Analogs based on this structural model that have the region various amounts of removed, yet retain N C termini in similar spatial orientation were designed. The gap formed removal residues (residues 8-17 or 7-20) was spanned with single 8-aminooctanoic acid residue (Aoc) further introduction...
Decreased left ventricle (LV) function caused by genetic mutations or injury often leads to debilitating and fatal cardiovascular disease. LV cardiomyocytes are, therefore, a potentially valuable therapeutical target. Human pluripotent stem cell-derived (hPSC-CMs) are neither homogeneous nor functionally mature, which reduces their utility. Here, we exploit cardiac development knowledge instruct differentiation of hPSCs specifically toward cardiomyocytes. Correct mesoderm patterning retinoic...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnticoagulant peptides. Nature of the interaction C-terminal region hirudin with a noncatalytic binding site on thrombinJohn L. Krstenansky, Thomas J. Owen, Mark T. Yates, and Simon MaoCite this: Med. Chem. 1987, 30, 9, 1688–1691Publication Date (Print):September 1, 1987Publication History Published online1 May 2002Published inissue 1 September 1987https://doi.org/10.1021/jm00392a030RIGHTS & PERMISSIONSArticle Views95Altmetric-Citations47LEARN...
MDL 28,050 is a decapeptide antithrombin agent that inhibits alpha-thrombin-induced fibrin clot formation by binding to non-catalytic site on alpha-thrombin. It the result of chemical and structural optimization functional domain leech anticoagulant, hirudin. In contrast contention polyanionic nature this C-terminal governs its interaction with alpha-thrombin, systematic study region has shown importance lipophilic residues for providing functionality necessary potent The development other...
A solid phase organic synthesis method has been developed for the preparation of substituted methylene malonamic acids and malonic ester mono 5. Two substituents are introduced into core molecule 5 by unsymmetrical acid derivatives 2, followed Knoevenagel condensation with aromatic or aliphatic aldehydes, giving resin-bound 4. Evaluation scope these reactions led to a 96-member library from set eight amines/alcohols (seven amines one alcohol) 11 aldehydes leading 88 malonamic/malonate 3....
Secondary structure is not typically observed for small peptides in solution. Several of the properties α‐helical are known which lead to stabilization structure. The utilization all factors important design model (MAP) reported. based on repeating eleven amino acid sequence, Glu‐Leu‐Leu‐Glu‐Lys‐Leu‐Leu‐Glu‐Lys‐Leu‐Lys (MAP 1–11 ). CD spectra these give evidence more content than has been reported any short peptide (< 18 acids) date. This tendency does require presence lipid or reduced...
Abstract Background Epstein-Barr Virus (EBV)-encoded RNAs (EBERs) are non-polyadenylated RNA molecules transcribed from the EBV genome by polymerase III (pol III). EBERs most abundant viral latent gene products, although precise mechanisms which is able to achieve such high levels of EBER expression not fully understood. Previously has been demonstrated induce transcription factors associated with expression, including pol and ATF-2. We have recently that EBV-encoded nuclear antigen-1...
Integrin binding to proteins often involves recognition of domains containing the arginine-glycine-aspartate (RGD) motif. Different affinities and specificities integrin-ligand protein interactions involve additional domains. The n.m.r. structure snake-venom echistatin suggested that C-terminal portion molecule might be important, in addition RGD domain, integrin glycoprotein IIbIIIa (GPIIbIIIa) [Saudek, Atkinson Pelton (1991) Biochem. 30, 7369-7372]. synthetic peptide, echistatin-(40-49),...
An idealized model amphipathic α-helical decapeptide was synthesized and tested for effcacy as a totally synthetic lung surfactant in simple mixtures with dipalmitoylphosphatidylcholine (DPPC). Quasi-static compliance restored to 92 ± 3% of the unlavaged value at pressure 5 cm H2O an vitro lavaged rat model. A sustained improvement gas exchange also observed when guinea pigs were treated vivo DPPC/peptide rapidly formed low surface tension films pulsating bubble surfactometer consistent...
Patients with hypertrophic cardiomyopathy, particularly young adults, can die from arrhythmia, but the mechanism underlying abnormal rhythm formation remains unknown. C57Bl6 × CBA/Ca mice carrying a cardiac actin ( ACTC) E99K (Glu99Lys) mutation reproduce many aspects of human including increased myofilament Ca2+ sensitivity and sudden death in proportion (up to 40%) (28-40 day old) animals. We studied hearts transgenic (TG; ACTC E99K) their non-TG (NTG) littermates when they were vulnerable...
C-terminal fragment analogues of the leech anticoagulant peptide hirudin represent a unique class thrombin inhibitors that blocks thrombin's cleavage fibrinogen but does not block catalytic site thrombin. In this paper, series synthetic peptides were prepared by solid-phase methodology to determine optimal N-terminal and position 56 functionalities for these hirudin. Inhibition fibrin clot formation in vitro was used as measure activity. minimal sequence necessary activity, hirudin56-64, an...
A solid-phase organic synthesis method has been developed for the preparation of 3-carboxypyrrolinones 9. Treatment polymer-bound malonic acid with amino alcohols afforded malonamide resin products 6. Benzyl and alkyl were prepared in solution via a two-step procedure without purification coupled to directly using capture strategy. Polymer loadings product conversions determined by direct cleavage resin-bound materials analysis 1H NMR spectroscopy an internal standard. malonamides TFA...