Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The drugs used to treat cancer today are a confusing array of compounds with differing origins, mechanisms of action, antitumour spectra, and toxicities. There are 5 chemically distinct types of alkylating agents; the prototypical agent is chlormethine (mustine) and the most recent addition is ifosfamide. Generally these drugs all work in the same fashion and their activity is cell cycle proliferation-dependent but phase-nonspecific. The antimetabolites consist of methotrexate, the pyrimidine and purine analogues, and pentostatin, an adenosine deaminase inhibitor and relative newcomer to the class. The individual mechanisms of action of these agents differ but cytotoxicity is generally cell cycle phase-specific. Naturally occurring antineoplastic agents include the vinca alkaloids, the antitumour antibiotics, 1-asparaginase, the epipodophyllotoxins, and homoharringtonine; it is the most diverse collection of compounds. For these drugs as well as the antimetabolites, the therapeutic and toxic effects often depend heavily on duration of exposure to the drug, an effect known as schedule dependency. Finally, the agents that do not fit one of the above categories are cisplatin (cis-platinum II) and its analogue carboplatin (which is being actively investigated), hydroxycarbamide (hydroxyurea), procarbazine, hexamethylmelamine, amsacrine, and mitoxantrone (mitozantrone). In the future we can expect not only the emergence of new antineoplastic drugs, but also further refinements in the use of existing drugs. We are beginning to understand the various types of resistance manifested by tumour cells. Our ability to use these potent and highly toxic agents safely should continue to improve.
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PMID:Antineoplastic drugs in 1990. A review (Part I). 219 Jul 92

Photo-switchable ion and enzyme sensors were fabricated by the use of glassy carbon electrode coated with nonactindoped or enzyme modified poly(vinyl chloride) (PVC) membranes. The ion sensor with nonactin-doped PVC membrane, which contained spirobenzopyran as the photosensitive dye, exhibited a potentiometric photoresponse to NH4+ ion in the solution. The dynamic range of the NH4+ ion sensor was 10(-7)--10(-3) M. Urea, adenosine, and asparagine sensors were prepared by coating the surface of the NH4+-ion sensor with urease, adenosine deaminase, and asparaginase membranes, respectively. These enzyme sensors could be used for determining the substrates at the micro mole level. The performance characteristics of these sensors were compared with those previously prepared membrane electrode sensors.
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PMID:Photo-switchable ion and enzyme sensors. Photoinduced potentiometric response of glassy carbon electrode coated with polymer or polymer/enzyme dual membrane. 263 77

In experiments with mongrel male rats the asparaginase and adenosine deaminase activities in the liver tissue and adenosine deaminase in blood serum were determined under different conditions of parenteral nutrition. The intraperitoneal administration of the preparations of parenteral nitrogen nutrition-aminosol and amikin (0.25 g of conditioned protein per 100 g of body weight) against a background of protein deficiency and exhaustion is shown to cause no changes as compared to the control of these enzymes activity in the liver tissue and blood serum. The asparaginase activity in the liver increases noticeably with the dose of aminosol and amikin up to 0.5 g of conditioned protein per 100 g of body weight and the adenosine deaminase activity undergo no essential changes. A statistically significant decrease in the adenosine deaminase activity is observed only under administration of aminosol against a background of protein deficiency. Under oral feeding of rats with amikin in the composition of protein-free (0.5 g of conditioned protein per 100 g of body weight), as distinct from its parenteral administration, the asparaginase activity in the liver is considerably lower. The adenosine deaminase activity in the liver and blood serum is not practically changed. A part of the nitrogen excreted from the organism with urea and ammonia under protein deficiency is supposed to be a product of deamination of endogenic purine and pyrimidine derivatives.
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PMID:[Dynamics of asparaginase and adenosine deaminase activity in the liver with intraperitoneal administration of aminosol and amikin preparations of parenteral nitrogen nutrition]. 680 84

The use of polymers for delivering peptide and protein drugs is described. Soluble-polymer technology attempts to bind a polymer to all sites on therapeutic protein molecules that cause the body to recognize the molecules as foreign. Goals include a stable linkage, water solubility, low immunogenicity, prolonged half-life, and intact biological activity. Polyethylene glycol (PEG)-adenosine deaminase (ADA), or pegademase bovine, has FDA-approved labeling as replacement therapy for ADA deficiency in patients with severe combined immunodeficiency disease who are not suitable candidates for bone marrow transplantation. Pegademase bovine reverses the toxic accumulation of adenosine and deoxyadenosine in adenosine deaminase-deficient cells, restoring the immune system. PEG-asparaginase (pegaspargase) has shown promise in patients with acute lymphocytic leukemia; allergic reactions have been minimal. Animal studies suggest that superoxide dismutase has potential use in conditions in which the body's ability to remove oxygen free radicals is reduced, such as burns and myocardial infarction; coupling with PEG may greatly increase the protein's half-life. Other PEG-conjugated proteins under investigation include PEG-catalase, PEG-uricase, PEG-honeybee venom, PEG-hemoglobin, and PEG-modified ragweed pollen extract. Dextran, albumin, DL-amino acids, and polyvinyl pyrrolidone have also been studied as protein carriers; most of the products created thus far have not shown much promise. The coupling of polymers to proteins has yielded protein drugs with intact biological activity and reduced immunogenicity, but much remains to be learned about this technology.
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PMID:Polymers for delivering peptides and proteins. 816 Jun 72

To determine whether the activities of certain hydrolases (arylesterase, beta-glucuronidase, cathepsin L, plasminogen activators, arginase, glutaminase, asparaginase and adenosine deaminase) are changed during pregnancy, three groups of 15 apparently healthy women (aged 18-38 years) in their first, second and third trimester of pregnancy were compared to a control group formed of 15 non-pregnant women of similar ages. Enzyme and specific activities gradually increased from the first to the end of the third trimester of pregnancy for arylesterase and beta-glucuronidase, these increases being statistically significant (P < 0.01) in comparison to controls. However, as regards cathepsin L and plasminogen activators, the greatest increase was found in the second trimester. Arginase, glutaminase and asparaginase activities were very low and not distinguishable from the controls. In conclusion, differences in the activities of several hydrolases have been found in the sera of healthy pregnant women in comparison to controls.
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PMID:Variation in serum arylesterase, beta-glucuronidase, cathepsin L and plasminogen activators during pregnancy. 893 58

Polymer conjugation is of increasing interest in pharmaceutical chemistry for delivering drugs of simple structure or complex compounds such peptides, enzymes and oligonucleotides. For long time drugs, mainly with antitumoral activity, have been coupled to natural or synthetic polymers with the purpose of increasing their blood permanence time, taking advantage of the increased mass that reduces kidney ultrafiltration. However only recently complex constructs were devised that exploit the 'enhanced permeability and retention' (EPR) effect for an efficient tumor targeting, the high molecular weight for adsorption or receptor mediated endocytosis and finally a lysosomotropic targeting, taking advantage of acid labile bonds or cathepsin susceptible polypeptide spacers between polymer and drug. New original, very active conjugates of this type, as those based on poly(hydroxyacrylate) polymers, are already in advanced state of development. Labile oligonucleotides, including antisense drugs, were also successfully coupled to polymers in view of an increased cell penetration and stabilization towards nucleases. However, the most active research activity resides in the field of polypeptides and proteins delivery, mainly for the two following reasons: first of all because a great number of therapeutically interesting compounds are now being produced by genetic engineering in large quantity and, secondly, because these products are difficult to administer to patients for several inherent drawbacks. Proteins are in fact easily digested by many endo- and exo-peptidases present in blood or in other body districts; most of them are immunogenic to some extent and, finally, they are rapidly excreted by kidney ultrafiltration. Covalent polymer conjugation at protein surface was demonstrated to reduce or eliminate these problems, since the bound polymer behaves like a shield hindering the approach of proteolytic enzymes, antibodies, or antigen processing cell. Furthermore, the increase of the molecular weight of the conjugate allows to overcome the kidney elimination threshold. Many successful results were already obtained in peptides and proteins, conjugated mainly to water soluble or amphiphilic polymers like poly(ethylene glycol) (PEG), dextrans, or styrenemaleic acid anhydride. Among the most successful are the conjugates of asparaginase, interleukin-2 or -6 and neocarcinostatin, to remind some antitumor agents, adenosine deaminase employed in a genetic desease treatment, superoxide dismutase as scavenger of toxic radicals, hemoglobin as oxygen carrier and urokinase and streptokinase as proteins with antithrombotic activity. In pharmaceutical chemistry the conjugation with polymers is also of great importance for synthetic applications since many enzymes without loss of catalytic activity become soluble in organic solvents where many drug precursors are. The various and often difficult chemical problems encountered in conjugation of so many different products prompted the development of many synthetic procedures, all characterized by high specificity and mild condition of reaction, now known as 'bioconjugation chemistry'. Bioconjugation developed also the design of new tailor-made polymers with the wanted molecular weight, shape, structure and with the functional groups needed for coupling at the wanted positions in the chain.
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PMID:Bioconjugation in pharmaceutical chemistry. 1051 Aug 47