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Prolidase, a Potential Enzyme Target for Melanoma: Design of Proline-Containing Dipeptide-like Prodrugs
The analyses indicated that prolidase might be a desirable enzyme target based on its differential expression in melanoma cancer cell lines and its high substrate specificity for dipeptides containing proline at the carboxy terminus. The results suggest the possibility of targeting prolidase with prodrugs of anticancer agents for enhanced selectivity....
Survival Factor-Like Activity of Small Peptides in Hybridoma and CHO Cells Cultures
Synthetic peptides containing three to six amino acid residues were previously shown to improve key parameters of monoclonal antibody-producing mouse hybridoma cultures. The aim of the current work was to investigate whether small peptides also exert analogous beneficial impact on a CHO-K1-derived cell line (XMK-111-10) engineered for production of the...
Brief Overview of BioMicroNano Technologies
This paper provides a brief overview of the fields of biological micro-electromechanical systems bioMEMs and associated nanobiotechnologies, collectively denoted as BioMicroNano. Although they are developing at a very rapid pace and still redefining themselves, several stabilized areas of research and development can be identified. Six major areas are delineated, and...
Some Items of Interest to Process R&D Chemists and Engineers
This white paper reports deals with some items of interest to process R&D chemists and engineers and further provides systematic and descriptive information about these items. They report how these various items can be prepared on multigram scale using chemical or enzymatic synthesis methodology. The paper explains each items with...
Recombinant Antibody Production by Perfusion Cultures of rCHO Cells in a Depth Filter Perfusion System
Recombinant Chinese hamster ovary cells, producing recombinant antibody against the human platelet, were cultivated in a depth filter perfusion system DFPS. When perfusion cultures with working volume of 1 L were operated at perfusion rates of 5/d and 6/d, volumetric antibody productivities reached values 28 and 34 times higher than...
Practical Process for the Air Oxidation of Cresols: Mechanistic Investigations
The catalytic air oxidation of p-cresol and 2, 6-di-tert-butyl-4- methylphenol to the corresponding benzaldehydes was investigated to determine the mechanism at work in these oxidation reactions. A number of intermediates and byproducts, mainly in the form of dimers, were observed during the course of the reactions, and their structures were...
Synthesis of Commercial Phosphodiesterase(V) Inhibitors
The literature syntheses including patents of three commercial phosphodiesterase V (PDE5) inhibitors (sildenafil, vardenafil, and tadalafil) are reviewed with particular emphasis on largescale manufacture. For each of these compounds, some impressive chemical development work has been reported. Further uses of these compounds are being proposed and investigated in the paper.
DioRaSSP: Diosynth Rapid Solution Synthesis of Peptides
The paper deals in developing a novel method for the large-scale manufacturing of peptides in solution called DioRaSSP. It combines the advantages of the homogeneous character of classical solution-phase synthesis with the generic character and the amenability to automation inherent to the solid-phase approach. DioRaSSP is characterized by the fact...
A Study of the Paterson Boron Aldol Reaction as Used in the Large-Scale Total Synthesis of the Anticancer Marine Natural Product (+)-Discodermolide
This white paper note discusses an optimization study of a key reagent controlled enantioselective boron enolate aldol reaction forming the C6-C7 bond and the C7 hydroxyl-bearing stereocenter in (+)-discodermolide. Conditions were found which increased the yield, decreased the excess of enolate necessary, and increased product stability with respect to the...
Practical Process for the Air Oxidation of Cresols: Evaluation of the Laboratory-Scale Oxidation Process
Mechanistic proposals and predictions made were evaluated by carrying out the catalytic air oxidation of p-cresol in an alternative solvent system, comprising either a mixture of ethylene glycol and acetic acid for oxidations under acidic conditions or ethylene glycol and water for oxidations under basic conditions. The results obtained in...
Investigation of Practical Routes for the Kilogram-Scale Production of cis-3-Methylamino-4-methylpiperidines
Two routes for the synthesis of cis-N-protected-3-methylamino- 4-methylpiperidine (3) were examined: a route hinging on the electrochemical oxidation of carbamate 1 to install a ketone at the 3 position of the piperidine followed by reductive amination disconnection A, and a route involving the hydrogenation of an appropriately functionalized pyridine (disconnection...
Purification and Characterization of an Anti-Apoptotic Protein Isolated From Lonomia Obliqua Hemolymph
In this work the anti-apoptotic properties of this hemolymph in Spodoptera frugiperda (Sf-9) cell culture were investigated. The presence or absence of apoptotic cells was characterized by light microscopy, flow cytometry, and agarose gel electrophoresis. Hemolymph was fractionated by several ion exchange and gel filtration chromatographic steps for identification of...
Effect of Increased Expression of Protein Disulfide Isomerase and Heavy Chain Binding Protein on Antibody Secretion in a Recombinant CHO Cell Line
The paper reveals that a human-antibody-producing recombinant CHO cell line did not increase its intracellular content of protein disulfide isomerase PDI and heavy chain binding protein BIP according to the increasing expression of antibody. It was also found that the intracellular assembly of light and heavy chain is a major...
Densities and Excess Molar Volumes for Acetone + Propionic Acid + Water From (283.15 to 323.15) K at Atmospheric Pressure
This paper presents experimental densities for the system acetone + propionic acid + water at atmospheric pressure from (283.15 to 323.15) K. A vibrating-tube densimeter provides density measurements over the entire composition range. The paper further presents a brief calculation of the excess volumes of the mixture and represents them...
Construction and Evaluation of Drug-Metabolizing Cell Line for Bioartificial Liver Support System
Focusing on drug metabolism in liver, the paper deals with the construction and evaluation of a drug-metabolizing bioartificial liver BAL support system. For further mimicking of liver metabolism, the human hepatoma-derived cell line HepG2 was transformed by the pBudCE-GS-CYP3A4 vector, which contains GS and drug-metabolizing CYP 3A4 genes. The constructed...
Glycosylation of Recombinant Antibody Therapeutics
The adaptive immune system has the capacity to produce antibodies with a virtually infinite repertoire of specificities. Recombinant antibodies specific for human targets are established in the clinic as therapeutics and represent a major new class of drug. Therapeutic efficacy depends on the formation of complexes with target molecules and...
A Facile and Scaleable Synthesis of ABT-239, a Benzofuranoid H3 Antagonist
A facile and scaleable synthesis of a potent and selective histamine H3 receptor antagonist, ABT-239 (1), was developed starting from commercially available 4'-hydroxy-biphenyl-4- carbonitrile (2). The synthesis comprised four chemical steps and a salt formation step with an overall yield of 40%. A highly selective monoiodination of a phenol was...
Thermodynamics of Phase and Chemical Equilibrium in a Strongly Nonideal Esterification System
In this study, the reaction equilibrium of the reversible esterification of acetic acid with 1-butanol giving 1-butyl acetate and water was investigated. The entire composition space including the miscibility gap was covered at temperatures relevant for technical processes (353.15 K to 393.15 K). The experiments were carried out in a...
Practical Synthesis of Triethylammonium ( Z)-2-[2-(Boc-amino)thiazol-4-yl]-2-(trityloxyimino)acetate, the Side Chain of Cefmatilen
A practical synthesis of triethylammonium Z-2-[2-(N-tertbutoxycarbonylamino) thiazol-4-yl]-2-triphenylmethyloxyimino acetate (1) which is the C-7 side chain of cefmatilen, a new cephalosporin antibiotic, is described. The conditions were optimized to control the impurity and to increase the yield. Selective acetylation of oxime group before tert-butoxycarbonylation reduced the amount of Boc2O. Compound 1...
Process Development and Scale-Up of a Selective Alpha1-Adrenoceptor Antagonist
A synthetic route to a potent and selective r-1-adrenergic receptor antagonist has been developed and demonstrated in a pilot plant. The route has been used in two pilot plant campaigns and has produced RO3203546 in 2.3 and 12.0 kg batch sizes. The first pilot plant campaign focused primarily on the...
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