A5054865970- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Protein purification and stability
- Viral Infectious Diseases and Gene Expression in Insects
- Synthesis and Characterization of Heterocyclic Compounds
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Advanced Biosensing Techniques and Applications
- Bacterial Genetics and Biotechnology
- CAR-T cell therapy research
- Pluripotent Stem Cells Research
- Carbohydrate Chemistry and Synthesis
- Synthesis and Reactions of Organic Compounds
- Hepatitis B Virus Studies
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- HER2/EGFR in Cancer Research
- Quinazolinone synthesis and applications
- CRISPR and Genetic Engineering
- Biotin and Related Studies
- Enzyme Structure and Function
- HIV/AIDS drug development and treatment
- DNA and Nucleic Acid Chemistry
- Hepatitis C virus research
Glenmark Pharmaceuticals (Switzerland)
2024
Institut Curie
2023
University of Cambridge
2007-2015
Wellcome Sanger Institute
2004-2009
Massachusetts Institute of Technology
1992-1999
University of Edinburgh
1993-1999
University of Birmingham
1991-1992
University of Hertfordshire
1982-1984
Guy's Hospital
1983
Abstract Background In the search for generic expression strategies mammalian protein families several bacterial vectors were examined their ability to promote high yields of soluble protein. Proteins studied included cell surface receptors (Ephrins and Eph receptors, CD44), kinases (EGFR-cytoplasmic domain, CDK2 4), proteases (MMP1, CASP2), signal transduction proteins (GRB2, RAF1, HRAS) transcription factors (GATA2, Fli1, Trp53, Mdm2, JUN, FOS, MAD, MAX). Over 400 experiments performed...
Abstract We have created a high quality phage display library containing over 10 human antibodies and describe its use in the generation of on an unprecedented scale. selected, screened sequenced 38,000 recombinant to 292 antigens, yielding 7,200 unique clones. 4,400 were characterized by specificity testing detailed sequence analysis data/clones are available online. Sensitive detection was demonstrated bead based flow cytometry assay. Furthermore, positive staining immunohistochemistry...
Abstract Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits efficacy immunotherapeutic approaches. The receptor expresses one two highly homologous chains [T β-chain constant (TRBC) domains 1 and 2] in mutually exclusive manner, making it promising target. Here we demonstrate specificity redirection by rational design using structure-guided...
Abstract During the last few years Antibody-Drug Conjugates (ADCs) have become one of most active and very promising therapeutic weapons. Lessons learned from traditional chemical conjugations (via lysine or cysteine residues antibodies) clinical studies developed ADCs recently paved way to improvement conjugation technologies. Use site-specific is considered as path for improving design development homogeneous with controlled Drug-Antibody ratio (DAR). Moreover, some these can be applied...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe synthesis and antiviral activity of some 4'-thio-2'-deoxy nucleoside analogsMichael R. Dyson, Paul L. Coe, Richard T. WalkerCite this: J. Med. Chem. 1991, 34, 9, 2782–2786Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://pubs.acs.org/doi/10.1021/jm00113a016https://doi.org/10.1021/jm00113a016research-articleACS PublicationsRequest reuse permissionsArticle...
Research Article| May 01, 2011 Geologic versus geodetic deformation adjacent to the San Andreas fault, central California Sarah J. Titus; Titus † 1Department of Geology, Carleton College, 1 N. College St., Northfield, Minnesota 55057, USA *E-mail: stitus@carleton.edu Search for other works by this author on: GSW Google Scholar Mark Dyson; Dyson Charles DeMets; DeMets 2Department Geoscience, University Wisconsin, 1215 W. Dayton Madison, Wisconsin 53706, Basil Tikoff; Tikoff Frederique...
The early phase of protein drug development has traditionally focused on target binding properties leading to a desired mode therapeutic action. As more therapeutics pass through the pipeline; however, it is clear that non-optimal biophysical can emerge, particularly as proteins are formulated at high concentrations, causing aggregation or polyreactivity. Such late-stage "developability" problems lead delay failure in traversing process. Aggregation propensity also correlated with increased...
Abstract Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report development ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. 1442 consists two anti-CD38 arms targeting distinct epitopes that preferentially drive binding tumor cells enable avidity-induced blocking proximal CD47 receptors on same cell while...
As an example for studies of contacts involved in complex biological systems, peptide ligands that bind to the core antigen hepatitis B virus (HBcAg) have been selected from a random hexapeptide library displayed on filamentous phage. Affinity-purified phage bearing aa sequence LLGRMK, or some related sequences, bound full-length truncated HBcAg but did not denatured HBcAg. The long (L), short (S), envelope polypeptide, when synthesized vitro system, firmly HBcAg, indicating interaction...
Notch signalling occurs via direct cell–cell interactions and plays an important role in linking the fates of neighbouring cells. There are four different mammalian receptors that can be activated by five cell surface ligands. The ability to inhibit specific would help identify roles individual family members potentially provide a means study control differentiation. Anti-Notch antibodies form single chain Fvs were generated from antibody phage display library selection on either ligand...
The construction of large libraries in mammalian cells allows the direct screening millions molecular variants for binding properties a cell type relevant or production. We have created up to 10 million clones displaying repertoire IgG-formatted antibodies on surface. TALE nucleases CRISPR/Cas9 were used integration antibody genes into single genomic locus, thereby rapidly achieving stable expression and transcriptional normalization. utility system is illustrated by affinity maturation...
To demonstrate the utility of phage display in generating highly specific antibodies, affinity selections were conducted on 20 related Src Homology 2 (SH2) domains (ABL1, ABL2, BTK, BCAR3, CRK, FYN, GRB2, GRAP2, LYN, LCK, NCK1, PTPN11 C, PIK3R1 PLCγ1 RASA1 SHC1, SH2D1A, SYK N, VAV1 and tandem ZAP70). The expressed Escherichia coli, purified used selection experiments. In total, 1292/3800 resultant antibodies shown to bind target antigen. Of 695 further evaluated specificity ELISAs against...
Adamalysin-like metalloproteinases with thrombospondin (TS) motifs (ADAMTS)-5 is the multi-domain metalloproteinase that most potently degrades aggrecan proteoglycan in cartilage and its activity implicated development of osteoarthritis (OA). To generate specific exosite inhibitors for it, we screened a phage display antibody library presence zinc-chelating active site-directed inhibitor GM6001 (Ilomastat) isolated four highly selective inhibitory antibodies. Two antibodies were mapped to...
In this report we present 21 instances in which live rubella virus was isolated from synovial fluid obtained 6 cases of inflammatory oligoarthritis or polyarthritis over a period 2 years the absence firm clinical evidence rubella. 3 (cases 1, 2, 6,) persistent predominantly affecting knee joints occurred adult women and one man, lasting to date 27, 29, 18 months respectively, these virions were found cells membrane. case boy 9 presented with an illness indistinguishable systemic variety...
We measured kinetic parameters in vitro and directly analyzed aminoacylation formylation levels vivo to study recognition of Escherichia coli initiator tRNA mutants by E. Met-tRNA synthetase transformylase. show that, addition the anticodon sequence, mutations "discriminator" base A73 also affect aminoacylation. An A73----U change has a small effect, but G73 or C73 significantly lowers Vmax/Kappm for leads appreciable accumulation uncharged vivo. Significantly, coupling mutation with G72,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformation of two 4'-thio-2'-deoxynucleoside analogs studied by 5000-MHz proton NMR spectroscopy and x-ray crystallography.Leo H. Koole, Janez Plavec, Hongying Liu, Beverly R. Vincent, Michael Dyson, Paul L. Coe, Richard T. Walker, George W. Hardy, S. Rahim, Jyoti ChattopadhyayaCite this: J. Am. Chem. Soc. 1992, 114, 25, 9936–9943Publication Date (Print):December 1, 1992Publication History Published online1 May 2002Published inissue 1 December...
A practical 7 step synthesis of benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-D-erythro-pentofuranoside from 2-deoxy-D-ribose is described and the product has been used in some 4′-thio-2′-deoxynucleosides which have potentially useful biological activity.
For many tRNAs, the discriminator base preceding CCA sequence at 3' end is important for aminoacylation. We show that influences stability of 1.72 pair onto which it stacked. Mutations from adenosine to cytidine or uridine make residue in C1-G72 mutant Escherichia coli initiator tRNAs more reactive toward sodium bisulfite, single-strand-specific reagent. The activity enzyme Met-tRNA transformylase these and other also consistent with destabilization vitro vivo. By influencing strength pair,...
Abstract Background A variety of approaches to understanding protein structure and function require production recombinant protein. Mammalian based expression systems have advantages over bacterial for certain classes but can be slower more laborious. Thus the availability a simple system rapid screening constructs or conditions mammalian would great benefit. To this end we coupled an efficient on transient transfection in HEK-293 EBNA1 (HEK-293E) suspension cells with dot blot method...
We describe a new method, which identifies protein fragments for soluble expression in Escherichia coli from randomly fragmented gene library.Inhibition of E. dihydrofolate reductase (DHFR) by trimethoprim (TMP) prevents growth, but this can be relieved murine DHFR (mDHFR).Bacterial strains expressing mDHFR fusions with the proteins green fluroscent (GFP) or EphB2 (SAM domain) displayed markedly increased growth rates TMP compared to insoluble (TK ketosteroid isomerase (KSI).Therefore, is...