A5072152749- Sleep and related disorders
- Sleep and Wakefulness Research
- Cell death mechanisms and regulation
- Signaling Pathways in Disease
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Sleep and Work-Related Fatigue
- Protein Kinase Regulation and GTPase Signaling
- Gender Roles and Identity Studies
- Biochemical and Molecular Research
- Health disparities and outcomes
- ATP Synthase and ATPases Research
- Protease and Inhibitor Mechanisms
- Migration, Aging, and Tourism Studies
- Work-Family Balance Challenges
- Employment and Welfare Studies
- Advanced NMR Techniques and Applications
- RNA and protein synthesis mechanisms
- Homelessness and Social Issues
- Neuroethics, Human Enhancement, Biomedical Innovations
- Peptidase Inhibition and Analysis
- Force Microscopy Techniques and Applications
- Molecular spectroscopy and chirality
- DNA and Nucleic Acid Chemistry
- Spectroscopy Techniques in Biomedical and Chemical Research
University of Surrey
2015-2024
Abbott (United States)
1993-2009
Abbott Fund
1995-2005
General Atomics (United States)
2004-2005
Neurocrine Biosciences (United States)
2004
Discovery Laboratories (United States)
1995-2000
Abbott (United Kingdom)
1994
Purdue University West Lafayette
1991-1992
Queen Elizabeth Hospital
1969
Ball State University
1967
A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together produce high-affinity ligands. The approach called “SAR by NMR” because structure-activity relationships (SAR) obtained from NMR. With this technique, compounds with nanomolar affinities for the FK506 binding were rapidly discovered tethering two ligands micromolar affinities. reduces amount chemical synthesis...
Heterodimerization between members of the Bcl-2 family proteins is a key event in regulation programmed cell death. The molecular basis for heterodimer formation was investigated by determination solution structure complex survival protein Bcl-xL and death-promoting region Bcl-2-related Bak. binding affinities mutant Bak peptides indicate that peptide adopts an amphipathic alpha helix interacts with through hydrophobic electrostatic interactions. Mutations full-length disrupt either type...
Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated tumor growth, pathogenesis, resistance to chemo- or radiotherapy. On the basis NMR structure a SMAC peptide complexed with BIR3 domain X-linked IAP (XIAP), novel series XIAP antagonists was discovered. The most potent compounds this bind baculovirus repeat 3 (BIR3) single-digit nanomolar affinity promote cell death several human cancer lines. In MDA-MB-231 breast mouse xenograft model, these...
Abstract The three‐dimensional structure of the anti‐apoptotic protein Bcl‐X L complexed to a 25‐residue peptide from death promoting region Bad was determined using NMR spectroscopy. Although overall is similar bound 16‐residue Bak (Sattler et al., 1997), forms additional interactions with . However, based upon site‐directed mutagenesis experiments, these contacts do not account for increased affinity 25‐mer compared 16‐mer. Rather, helix propensity primarily responsible its greater Based...
With the use of an NMR-based method, potent (IC50 < 25 nM) nonpeptide inhibitors matrix metalloproteinase stromelysin (MMP-3) were discovered. The called SAR by NMR (for structure−activity relationships nuclear magnetic resonance), involves identification, optimization, and linking compounds that bind to proximal sites on a protein. Using this technique, two ligands weakly (acetohydroxamic acid, KD = 17 mM; 3-(cyanomethyl)-4'-hydroxybiphenyl, 0.02 mM) identified. On basis NMR-derived...
The inhibitor of apoptosis proteins (IAPs) regulate the caspase family cysteine proteases, which play an important role in execution programmed cell death. Human X-linked protein (XIAP) is a potent caspases-3, -7, and -9. Here we show that Bir3 domain minimal region XIAP needed for caspase-9 inhibition. three-dimensional structure XIAP, determined by NMR spectroscopy, resembles classical zinc finger consists five α-helices, three-stranded β-sheet, atom chelated to three cysteines one...
D rug discovery is a difficult and time-consuming process that involves the identification of potent therapeutic agents with good bioavailability, metabolic stability, low toxicity. An important first step in this molecules bind high affinity
Abstract The study of sleep has been neglected within sociology, yet may provide insights into fundamental aspects the nature gender inequalities. This article examines how, for couples with children, is influenced by gendered caring. A key concern not only who gets up to care children's physical needs at night, but whether this changes women's increased role in labour market. Of also how caring older as opposed young impact on parents’ sleep. analyses qualitative data from an ESRC funded...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn the evaluation of interproton distances for three-dimensional structure determination by NMR using a relaxation rate matrix analysisCarol Beth Post, Robert P. Meadows, and David G. GorensteinCite this: J. Am. Chem. Soc. 1990, 112, 19, 6796–6803Publication Date (Print):September 1, 1990Publication History Published online1 May 2002Published inissue 1 September...
Purpose The purpose of this study is to deepen our understanding the well-being transient organizations/groups and use develop a novel conceptual framework gig worker during times crisis. Design/methodology/approach A qualitative approach was adopted combining in-depth semi-structured interviews daily diaries. Twenty-two workers working in sharing economy were recruited. Thematic analysis conducted for diary interview data. Findings findings illustrate complex picture workers’ four...
SummaryAim: To compare the central and peripheral H1 inhibitory effects of acute sub-chronic doses levocetirizine (l-CTZ), cetirizine (CTZ), loratadine (LOR) promethazine (PRM) versus placebo, using a battery psychomotor cognitive tests together with measures weal flare reaction. PRM was included in study as positive internal control to validate sensitivity psychometric test CNS various treatments.Methods: Twenty healthy volunteers (18–50 years) received l-CTZ 5 mg, CTZ 10 LOR 30 mg placebo...