Synthesis and Properties of New Nucleotide Analogues Possessing Squaramide Moieties as New Phosphate Isosters

Abstract

Keywords: Squaric acid / Acidity / Nucleotide analogues / Cyclic nucleotide analogues New analogues of 2Ј-deoxynucleotides and ribonucleotides incorporating a unique squaramide structure were synthesized. Because of the strong acidity of this moiety (pK a = 2.3), these nucleotide analogues exist in a monoanionic form, which can be regarded as an electronic isoster of 5Ј-nucleotides under physiological conditions. The synthesis of the nucleotide analogues was achieved through the condensation of 5Ј-or 3Ј-aminonucleosides with dimethyl squarate, whilst the selective removal of the methyl group was effectively accomplished by treatment with sodium bromide. In addition,

Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation

“…Squaric acid possesses similar charge distribution, polarity, and acidic properties as phosphoric acid, hence the squaramide group could represent an isostere for the phosphate group [29], [30]. Similarly, sulfonamide derivatives have been reported as phosphate mimics in the design of tyrosine phosphatase inhibitors [31].…”

“…The amine 1e was condensed either with dimethyl squarate [29] to afford the squaramide derivative 2 or with polar sulfonyl chlorides to furnish the sulfonamide derivatives 5 . These intermediates were N 7 -alkylated using a range of alkyl or aryl bromides [14] to provide the methyl squaramides 3 and sulfonamides 6 .…”

Phosphate bioisostere containing amphiphiles: a novel class of squaramide-based lipids

“…[8][9][10][11] The squaramide moiety has extensive applications including bioisosteres for various acidic functional groups. 9, 10 A varieties of squaramide-based compounds are used in chemistry and medicinal chemistry related applications.…”

Mechanism of Action of Cyclic Oligosquaramides on DPPC Phospholipid Monolayers

“…[3] Squaramide derivatives might act as cyanoguanidine replacements, [4] functional inhibitors of HIV-1 in cells, [5] headgroups for metalloprotease inhibitors, [6] aminoacid analogues in bioactive peptides, [7] arginine mimetic agent, [8] antagonists of the G protein-coupled receptors CXCR1 and CXCR2, [9] and as formation agents of carbohydrate-oligonucleotide conjugates. [10] The squaramide derivatives have been appointed also as isosteres for phosphate [11] and aminoacids. [12] In spite of the impressive results of squaramides in the biological tests, there are no reports on the molecular mechanism of action of squaramides at biological membranes.…”