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Peter B. Russell

Bio: Peter B. Russell is an academic researcher from Indiana University. The author has contributed to research in topics: Vaccinia & Nucleic acid. The author has an hindex of 17, co-authored 40 publications receiving 1098 citations.
Topics: Vaccinia, Nucleic acid, Virus, Alkyl, Aryl

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TL;DR: A study was begun in these laboratories, in 1942, of the relationship between chemical structure and the ability of certain pyrimidine* derivatives to serve as precursors for or to modify nucleic acid synthesis, and it has become known that two purines do contribute to the nucleic Acid purine of mammalian tissues, and the hypothesis becomes subject to modification on this account.
Abstract: A study was begun in these laboratories, in 1942, of the relationship between chemical structure and the ability of certain pyrimidine* derivatives to serve as precursors for or to modify nucleic acid synthesis. Since only brief accounts of small portions of this work have been published to the present paper is to be regarded as a preliminary report of the work as n whole. It was felt that such studies might lead to fundamental knowledge of the roles of pyrimidine and purine bases in growth, and of the part played by folk acid in the synthesis of these bases. It was felt also that new chemotherapeutic agents might be discovered by this means since, it was argued, parasitic tissues in general depend for survival on a more rapid growth, hence a more rapid synthesis of nucleic acid, than that of the host tissues. This argument applies equally well to bacterial, viral, rickettsial, and neoplastic diseases, so that, in a sense, one might say we have been searching for the philosopher’s stone, the universal panacea, of the ancients. A distinct advantage of antipurines and antipyrimidines as chemotherapeutic agents seemed to lie in the fact that the requirements of bacteria, at least, appeared to be qualitatively different from those of mammalian tissues. A considerable number of microorganisms6 were known to require preformed pyrimidines and/or purines for growth, whereas the evidence available a t that time indicated that purine and pyrimidine bases played no role in mammalian nucleic acid synthesis.6 In the interim, of course, it has become known that two purines, adenine7rR and 2,6-diaminop~rine,~ do contribute to the nucleic acid purine of mammalian tissues, and the hypothesis becomes subject to modification on this account. The effect of thymine in nutritional macrocytic anemia, sprue, and pernicious anemialo indicates that some metabolic role may have to be postulated for this pyrimidine base in the face of the studies with isotopically tagged thymine, which indicated only a catabolic elimination and no retention of exogenous thymine.6 It is conceivable that guanine, uracil, and cytosine may have metabolic roles which remain undetected in similar studies because of low turnover rates or for other reasons. The choice of Lactobacillus casei as a model biological system for the study of pyrimidine analogs was based on the known requirement of this microorganism for folk acid and the role of thymine and guanine in the satisfaction of this growth requirement:‘ This allows a study of the activity of each substance in a number of different ways in the same microorganism. TABLE 1 shows the six media used for study and the effects of various substances in each of the media. The media contain thymine or

107 citations


Cited by
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TL;DR: In this paper, the reactions of RuCl2(PPh3)3 with a number of diazoalkanes were surveyed, and alkylidene transfer was observed for RCHN2 and various para-substituted aryl diazalkanes p-C6H4X CHN2.
Abstract: The reactions of RuCl2(PPh3)3 with a number of diazoalkanes were surveyed, and alkylidene transfer to give RuCl2(CHR)(PPh3)2 (R = Me (1), Et (2)) and RuCl2(CH-p-C6H4X)(PPh3)2 (X = H (3), NMe2 (4), OMe (5), Me (6), F (7), Cl (8), NO2 (9)) was observed for alkyl diazoalkanes RCHN2 and various para-substituted aryl diazoalkanes p-C6H4XCHN2. Kinetic studies on the living ring-opening metathesis polymerization (ROMP) of norbornene using complexes 3−9 as catalysts have shown that initiation is in all cases faster than propagation (ki/kp = 9 for 3) and that the electronic effect of X on the metathesis activity of 3−9 is relatively small. Phosphine exchange in 3−9 with tricyclohexylphosphine leads to RuCl2(CH-p-C6H4X)(PCy3)2 10−16, which are efficient catalysts for ROMP of cyclooctene (PDI = 1.51−1.63) and 1,5-cyclooctadiene (PDI = 1.56−1.67). The crystal structure of RuCl2(CH-p-C6H4Cl)(PCy3)2 (15) indicated a distorted square-pyramidal geometry, in which the two phosphines are trans to each other, and the alkyli...

1,957 citations

Journal ArticleDOI
TL;DR: Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.
Abstract: The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents. It was, however, four World War II-related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.

1,388 citations

Journal ArticleDOI
TL;DR: The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort.
Abstract: Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

1,107 citations

Journal ArticleDOI
12 Aug 2011-Cancers
TL;DR: A review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine).
Abstract: Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

580 citations