DNA Derivatives

Contig A group of pieces of DNA, derived from a cloning experiment (often a series ( ESTs, see below), that represent overlapping regions of a chromosome... 

The phosphorodithioates DNA derivatives have been shown to bind specifically to complementary DNA or ENA sequences to form stable adducts. Because they are also highly resistant to degradation by cellular exonucleases, these derivatives can be useful both for appHcations in research and as therapeutic dmgs. Phosphorodithioate DNA has been shown to stimulate Rnase H activity in nuclear cell extracts and is a potent inhibitor of HIV type-1 reverse transcriptase (56). 

Quality of Biotechnological Products Analysis of the Expression Construct in Cells Used for Production of r-DNA-Derived Protein Products... 

Huang, B., Gudi, R., Wu, P., Harris, R.A., Hamilton, J. and Popov, KM. (1998a) Isoenzymes of pyruvate dehydrogenase phosphatase. DNA-derived amino acid sequences, expression, and regulation. Journal of Biological Chemistry 273, 17680-17688. 

Conventional pharmaceutical development has been estimated to costs roughly between 100 million and 800 million per product, and takes over 12 years. The development of conventional vaccines may be somewhat less costly, although new recombinant DNA-derived subunit vaccines produced in fermentation-based systems are likely to be similar to protein pharmaceuticals in development costs. At present, none of the major pharmaceutical companies is directing funding towards the development of plant-derived vaccines for infectious diseases. This may reflect ... 

Bristow, A. 1993. Recombinant DNA derived insulin analogues as potentially useful therapeutic agents. Trends in Biotechnology 11, 301-305. 

Goldenberg, M.M., "Trastuzumab, a Recombinant DNA Derived Monoclonal Antibody, a Novel Agent for the Treatment of Metastatic Breast Cancer," Clin. Ther., 21, 309-318 (1999). 

Quality of biotechnology products, analysis of the expression construct in cells used for production of r-DNA derived protein product Quality of biotechnological products stability testing of biotechnological/Biology products Availability of Draft Guideline on Quality of... 

Stebbing, N. and Week, P.K. (1984). Preclinical assessment of biological properties of recombinant DNA-derived human interferons. In Recombinant DNA Products Insulin, Interferon and Growth Hormone, (Bollon, A.P., Ed.). CRC Press, Boca Raton, FL. 

Ling V., Guzzetta A.W., Canova-Davis E., Stults J.T., Hancock W.S., Covey T.R., and Shushan B.I. (1991), Characterization of the tryptic map of recombinant DNA derived tissue plasminogen activator by high-performance liquid chromatography-electrospray ionization mass spectrometry, Anal. Chem. 63, 2909-2915. 

There are many examples of ELIS As used for detecting host cell impurities in the literature. Pauly et al.12 developed an ELISA to detect impurities in erythropoietin that had a detection limit of around 0.05 ng/ml. SDS polyacrylamide gel and Western blot analysis were used to confirm the spectrum of proteins detected and to demonstrate the specificity of the antibody preparation. Anicetti et al.14 describe an assay for the detection of E. coli proteins in recombinant DNA-derived human growth hormone. Whitmire and Eaton15 report on an immuno-ligand assay for quantitation of process-specific E. coli host cell contaminant proteins in a recombinant bovine somatotropin. 

Pauly, J.U., B. Siebold, R. Schulz, W. List, G. Luben, and F.R. Seiler. (1990). Development of an ELISA for the detection and determination of contaminating proteins in recombinant DNA derived human erythropoietin. Behring Inst Mitt 86 192-207. 

Sunday, B. R., Sydor, W., Guariglia, L. M., Obara, J., and Mengisen, R. (2003). Process and product monitoring of recombinant DNA-derived biopharmaceuticals with high-performance capillary electrophoresis./. Capillary Electrophor. 8, 87—99. 

Chakel, J. A., Erno, J., Hancock, W. S., and Swedberg, S. A. (1997). Analysis of recombinant DNA-derived glycoproteins via high-performance capillary electrophoresis coupled with off-line matrix-assisted laser desorption ionization time-of-fiight mass spectrometry. /. Chromatogr. B 689, 215—220. 

Presented here is a concise description of surface immobilization of DNA, oligonucleotides, and DNA derivatives by adsorption onto carbonaceous materials, and the properties of the DNA layer adsorbed on carbonaceous solid phase. 

To take advantages of the unique properties of CNTs, a general approach is the immobilization of DNA on CNTs and the further immobilization of the DNA-modified CNTs on an easier-to-handle pure conductor, e.g., GC [26], Ft [121], Au [ 122]. Another approach consists of the prior modification of the pure conductor (GC) with the CNTs through dry-adsorption and the further DNA or DNA derivatives adsorption on the CNT-modified surface [123-125]. 

The ultraviolet irradiation of DNA produces two photoproducts from thymine. The major product is identical with thymine ice-dimer (cis-syn, LXXVa), and accounts for 91 per cent of the DNA-derived photoproducts [541, 542]. A uracil-thymine dimer is also obtained in smaller quantity, which arises from deamination of a cytosine-thymine dimer [543, 544]. 

Orotic acid readily forms dimers even when irradiated in liquid medium [582, 583]. 5-Bromouracil (5-BrU) in DNA is dehalogenated, rather than forming cyclobutane-type dimers. Such DNA derivatives are more sensitive to ultraviolet irradiation than normal DNAs [584-594], Irradiation of 5-bromo-uracil and derivatives in aqueous medium produces 5,5 -diuracil [590, 591]. However, derivatives such as 3-sbutyl-5-bromo-6-methyluracil have been reported to yield cyclobutane dimers either by irradiation of frozen aqueous solutions, or by catalysis with free radical initiators, such as aluminium chloride, ferric chloride, peroxides or azonitriles [595]. 5-Hydroxymethyluracil is reported to dimerize very slowly in frozen water at 2537 A [596]. The fundamental research in the photochemistry of the nucleic acids, the monomeric bases, and their analogues has stimulated new experiments in certain micro-organisms and approaches in such diverse fields as template coding and genetic recombination [597-616]. 

A sample of total DNA derived from the cells in which the product is produced is then radiolabelled with using the process of nick translation. It is heated to 90°C (promotes... 

Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody used in the treatment of chronic lymphocytic leukemia and T-cell lymphoma. It targets CD52, a protein present on the surface of mature lymphocytes. Alemtuzumab has been associated with infusion-related events including hypotension, rigors, fever, shortness of breath, bron-chospasm, chills, and/or rash. Also reported were syncope, pulmonary infiltrates, cardiac arrhythmias, myocardial infarction and cardiac arrest. 

In 1996, about 10 years after the introduction of the first recombinant DNA product for human use, the FDA modified and streamlined the approval process for biotechnology products considered to be well characterized. These modifications, in essence, established the direction of how biologic macromolecules are researched and developed today in biotechnology-based and traditional pharmaceutical companies [2]. Well-characterized biotechnology products include (1) synthetic peptides consisting of fewer than 20 amino acids, (2) monoclonal antibodies and derivatives, and (3) recombinant DNA-derived products. Anticipating future developments, the FDA is also prepared to consider DNA plasmid products as well-characterized when the first medicinal in this class is submitted for approval. CBER now approves well-characterized biopharmaceuticals under the BLA process [3]. 

A. General description Denileukin dif-titox is a recombinant, DNA-derived, interleukin-2 receptor specific ligand, cytotoxic fusion protein consisting of diphtheria toxin fragments A and B fused to interleukin-2. It is produced by expression of a recombinant fusion protein in Escherichia coli that contains nucleotide sequences for human interleukin-2, and sequences for the enzymatically active fragment A of diphtheria toxin and the membrane-translocating portion of diph-... 

Kaplan, S.L., L.E. Underwood, G.P August, J.J. Bell, S.L. Blethen, R.M. Blizzard, D.R. Brown, T.P Foley, R.L. Hintz, N.J. Hopwood, et al.. Clinical studies with recombinant-DNA-derived methionyl human growth hormone in growth hormone deficient children. Lancet, 1986.1(8483) 697-700. 

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