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Phosphinic Acid Compounds in Biochemistry, Biology and Medicine

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Abstract:

This review summarizes our knowledge of biochemical, biological and medical applications and properties of phosphinic acid compounds. Phosphinic acid compounds (phosphinates) are derivatives of phosphinic acid H 2 P(O)(OH). The major attention of this article is focused on applications of phosphinates of a pseudopeptide character, however interesting examples of phosphinates of a non-peptide nature are mentioned too. Phosphinic acid peptides (phosphinic pseudopeptides) are peptide isosteres where one peptide bond is substituted by the nonhydrolysable phosphinate moiety -P(O)(OH)-CH 2 - or -P(O)(OH)-. This substitution represents a very convenient mimic of a substrate in the transition state for at least two distinct classes of hydrolytic enzymes, Zn-metalloproteinases and aspartic acid proteinases. In this review we discuss about thirty different protein targets for which the phosphinates have found applications as modulators of their functions in vitro and or in vivo. These proteins are mainly proteinases, however other types of proteins such as transferases, synthetases, ligases or even receptors are also discussed. Genome sequencing projects have been identifying protein sequences faster than it is possible to discover their functions. The development of combinatorial chemistry in the past few years has boosted up the interest in the use of chemistry to address biological problems. We believe that phosphinates, especially in conjunction with combinatorial chemistry approaches, can represent an extremely versatile tool in the search for proteome and its function.
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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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