Three Efficient Methods for Preparation of Coelenterazine Analogues

The growing popularity of bioluminescent assays has highlighted the need for coelenterazine analogues possessing properties tuned for specific applications. However, the structural diversity of known coelenterazine analogues has been limited by current syntheses. Known routes for the preparation of coelenterazine analogues employ harsh reaction conditions that limit access to many substituents and functional groups. Novel synthetic routes reported here establish simple and robust methods for synthesis and investigation of structurally diverse marine luciferase substrates. Specifically, these new routes allow synthesis of coelenterazine analogues containing various heterocyclic motifs and substituted aromatic groups with diverse electronic substituents at the R² position. Interesting analogues described herein were characterized by their physicochemical properties, bioluminescent half‐life, light output, polarity and cytotoxicity. Some of the analogues represent leads that can be utilized in the development of improved bioluminescent systems.     

Synthesis and medicinal importance of oxicams and their analogues

The biological and medicinal properties of oxicams and its analogues are attracting attention of chemist aimed at developing synthetic routes to these heterocycles. This review focuses on the synthesis and medical importance of oxicams and their analogues.     

D-luciferin analogues: a multicolor toolbox for bioluminescence imaging

Colorful mixture: Three types of luciferin analogues, that is, alkylaminoluciferins, aminoselenoluciferin, and luciferins with a benzimidazole scaffold, have been reported. These analogues show excellent bioluminescent properties and great potential in bioluminescence imaging.     

Fluorinated amino acids: compatibility with native protein structures and effects on protein-protein interactions

Fluorinated analogues of the canonical α-L-amino acids have gained widespread attention as building blocks that may endow peptides and proteins with advantageous biophysical, chemical and biological properties. This critical review covers the literature dealing with investigations of peptides and proteins containing fluorinated analogues of the canonical amino acids published over the course of the past decade including the late nineties. It focuses on side-chain fluorinated amino acids, the carbon backbone of which is identical to their natural analogues. Each class of amino acids--aliphatic, aromatic, charged and polar as well as proline--is presented in a separate section. General effects of fluorine on essential properties such as hydrophobicity, acidity/basicity and conformation of the specific side chains and the impact of these altered properties on stability, folding kinetics and activity of peptides and proteins are discussed (245 references).     

Development of bacteriorhodopsin analogues and studies of charge separated excited states in the photoprocesses of linear polyenes

Development of bacteriorhodopsin (bR) analogues employing chromophore substitution technique for the purpose of characterizing the binding site of bR and generating bR analogues with novel opto-electronic properties for applications as photoactive element in nanotechnical devices are described. Additionally, the photophysical and photochemical properties of variously substituted diarylpolyenes as models of photobiologically relevant linear polyenes are discussed. The role of charge separated dipolar excited states in the photoprocesses of linear polyenes is highlighted.     

The synthesis and properties of fluoro-substituted analogues of 4-butyl-4′-[(4-butylphenyl)ethynyl]biphenyls

The synthesis of 4-butyl-4′-[(4-butyl-2,6-difluorophenyl)ethynyl]biphenyl and its higher fluorinated analogues is presented and discussed. Correlations between molecular structure and mesomorphic properties for presented compounds as well as other known from the literature analogues have been drawn. The dielectric study of four synthesised compounds and their mixtures are presented and discussed. Trifluoro-substituted analogues are trade off between low dielectric anisotropy of difluorinated compounds and lower clearing points of tetrafluorinated ones.     

Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues

The inositol pyrophosphate messengers (PP‐InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP‐InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non‐hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal‐coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP‐InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions.     

Synthesis of imidazolo analogues of the oxidation-reduction cofactor pyrroloquinoline quinone (PQQ)

Parallel syntheses of 2-hydro-, 2-methyl-, and 2-methoxycarbonylimidazo-7,9-dimethoxycarbonyl analogues of the oxidation-reduction cofactor pyrroloquinoline quinone [4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid] have been developed. The properties of the imidazolo analogues in relation to the corresponding pyrrole analogues will be important in assessing the origins of catalysis and biological activity in the cofactor, which has recently been shown to be a vitamin.     

Global government applications of analogues,SARs and QSARs to predict aquatic toxicity,chemical or physical properties,environmental fate parameters and health effects of organic chemicals

Faced with the need to predict physical and chemical properties, environmental fate, ecological effects and health effects of organic chemicals in the absence of experimental data, several Government organizations have been applying analogues, Structure Activity Relationships (SARs) and Quantitative Structure Activity Relationships (QSARs) to develop those predictions. To establish some benchmarks for monitoring future increases in applications of analogues, SARs and QSARs by global Government organizations, this paper describes the current applications of analogues, SARs and QSARs by Australian, Canadian, Danish, European, German, Japanese, Netherlands, and United States Government organizations to predict physical and chemical properties, environmental fate, ecological effects and health effects of organic chemicals.     

Site-specific incorporation of tryptophan analogues into recombinant proteins in bacterial cells

A designed yeast phenylalanyl-tRNA synthetase (yPheRS (T415G)) activates four tryptophan (Trp) analogues (6-chlorotryptophan (6ClW), 6-bromotryptophan (6BrW), 5-bromotryptophan (5BrW), and benzothienylalanine (BT)) that are not utilized by the endogenous E. coli translational apparatus. Introduction of yPheRS (T415G) and a mutant yeast phenylalanine amber suppressor tRNA (ytRNAPheCUA_UG) into an E. coli expression host allowed site-specific incorporation of three of these analogues (6ClW, 6BrW, and BT) into recombinant murine dihydrofolate reductase in response to amber stop codons with at least 98% fidelity. All three analogues were introduced at the Trp66 position in the chromophore of a cyan fluorescent protein variant (CFP6) to investigate the attendant changes in spectral properties. Each of the analogues caused blue shifts in the fluorescence emission and absorption maxima. The CFP6 variant bearing BT at position 66 exhibited an unusually large Stokes shift (56 nm). An expanded set of genetically encoded Trp analogues should enable the design of new proteins with novel spectral properties.     

Structure-function relationships in glutathione and its analogues

The results are presented of measurements of protonation constants (potentiometry and NMR), UV spectroscopic properties and redox potentials of GSH and its five analogues, which are modified at the C-terminal glycine residue (gammaGlu-Cys-X, X = Gly, Gly-NH2, Gly-OEt, Ala, Glu, Ser). Strong linear correlations were found between various properties of the thiol and other functions of these peptides. These results allow discussion of the relationships between the structures and properties in glutathione and its analogues, and provide a novel chemical background for the issue of control of GSH reactivity.     

Inorganic,Organometallic, and Organic Analogues of Carbenes

This review deals with inorganic, organometallic, and organic compounds, as well as with elements, that on the basis of their electronic structure and their reactions can be regarded formally as analogues of carbenes. These “carbene analogues” include in particular the compounds of monovalent boron, aluminum, nitrogen, and phosphorus; those of divalent silicon, germanium, tin, and lead; atomic oxygen; atomic sulfur; and atomic selenium. The preparation and chemical properties of the carbenes and their analogues are compared.     

Global Government applications of analogues,SAR s and QSAR s to predict aquatic toxicity,chemical or physical properties,environmental fate parameters and health effects of organic chemicals

Faced with the need to predict physical and chemical properties, environmental fate, ecological effects and health effects of organic chemicals in the absence of experimental data, several Government organizations have been applying analogues, Structure Activity Relationships (SARs) and Quantitative Structure Activity Relationships (QSARs) to develop those predictions. To establish some benchmarks for monitoring future increases in applications of analogues, SARs and QSARs by global Government organizations, this paper describes the current applications of analogues, SARs and QSARs by Australian, Canadian, Danish, European, German, Japanese, Netherlands, and United States Government organizations to predict physical and chemical properties, environmental fate, ecological effects and health effects of organic chemicals.     

Enzymatic synthesis of caged NADP cofactors: aqueous NADP photorelease and optical properties

The synthesis of caged NADP analogues 18, 19, and 20 has been accomplished by utilizing the transglycosidase activity of solubilized NAD glycohydrolase (porcine brain) to incorporate caged nicotinamides 2, 3, and 4 into NADP. The synthesis of several nicotinamides modified at the carboxamide with o-nitrobenzyl photolabile groups is demonstrated as well as their potential for enzymatic transglycosidation. These results further demonstrate the feasibility of direct enzymatic transglycosidation of sterically hindered substrates into NAD(P), although high nicotinamide analogue water solubility was found to be a necessary trait for yield enhancement with certain analogues. Caged analogues were surveyed under aqueous conditions for net NADP photorelease, while the UV and fluorescent properties of both analogues and their photobyproducts were assessed for compatibility with systems that rely on optical monitoring of enzyme activity. A highly water-soluble alpha-methyl-o-nitrobenzyl group 8 was developed for the synthesis of 20 in order to enhance net NADP photorelease. Compound 20 demonstrated a high 75% net NADP photoreleased without substantial UV optical blackening or fluorescent byproducts. Analogues 18 and 19 were shown by ESI/MALDI-MS to photogenerate primarily adducts of NADP with deleterious UV and fluorescent properties. Our work stresses the superior release properties conferred by alpha-methyl substitution on aqueous carboxamide photorelease from o-nitrobenzyl compounds.     

Synthetic studies of carzinophilin. Part 4: Chemical and biological properties of carzinophilin analogues

Chemical and biological properties of carzinophilin congeners obtained in the course of our synthetic studies were investigated. These studies revealed feasibility for the use of some analogues as a double alkylating agent. Further, analogues carrying the naphthalene and the epoxide parts were found to show remarkable in vitro cytotoxicity and in vivo antitumor activity.     

Synthesis and antifungal activity of rhodopeptin analogues. 2. Modification of the west amino acid moiety

Structure-activity relationships of the west amino acid modified analogues of rhodopeptins, novel antifungal tetrapeptide isolated from Rhodococcus species Mer-N1033, have been investigated. Among the analogues synthesized, 2,2-difluoro and 2-hydroxy derivatives retained the antifungal activity with better physical properties, i.e., solubility or acute toxicity.     

Studies on the Synthesis of Di‐ and Trisaccharide Analogues of Moenomycin A. Modifications in Unit E and in the Lipid Part

Routes allowing the synthesis of moenomycin analogues with one modified sugar component and with new lipid parts were developed (see 10c, 12c, 16b , and 20b in Schemes 2–4). It is anticipated that such analogues will be useful for studying the mode of action of the moenomycin‐type transglycosylase inhibitors in detail and for preparing analogues with improved pharmacokinetic properties.     

Click fleximers: a modular approach to purine base-expanded ribonucleoside analogues

The synthesis of nucleoside analogues incorporating 4-(5-pyrimidinyl)-1,2,3-triazole aglycons as expanded purine nucleobase mimics were accessed using the copper-catalyzed azide-alkyne Huisgen cycloaddition between a ribosyl azide and 5-alkynylpyrimidines. Depending on the nature of the alkyne employed, other nucleoside analogues that possess fluorescence or potential metal-binding properties were prepared. Computational studies were undertaken on the purine analogues and indicate that the heterocycles of the unfused nucleobase prefer a coplanar arrangement and the anti-glycosidic conformer is favoured in most instances.     

Oligodeoxyribonucleotide analogues with bridging dimethylene sulfide,sulfoxide, and sulfone groups. Toward a second-generation model of nucleic acid structure

Short DNA analogues with bridging dimethylene sulfide, sulfoxide, and sulfone groups replacing the phosphate diesters (S-DNAs) were synthesized from building blocks prepared via two routes, both starting from D-glucose. Building blocks for RNA analogues were prepared by stereoselective introduction of nucleobase into a 2'-acylated ribose analogue. The ribose analogues were converted to deoxyribose analogues by replacement of a 3'-OH group by a thioacetyl unit, followed by photolytic deoxygenation or radical-based 2'-deoxygenation. DNA analogues joined via CH(2)(-)S-CH(2) units were prepared by S(N)2 displacement of a 6'-mesyl group on one building block using a thiolate nucleophile of another. 4,4'-Dimethoxytrityl protection and deprotection schemes were established for both the thiol and hydroxyl groups. The corresponding sulfoxide DNA analogues were obtained by oxidation with hydrogen peroxide. Sulfone DNA analogues were obtained by oxidation of the sulfide DNA with persulfate or hydrogen peroxide in the presence of a titanium silicate catalyst. The physical properties of several representative oligonucleotide analogues were examined, and interpreted in light of a "second-generation" model for DNA strand-strand recognition, a model that emphasizes the role of the polyanionic backbone in diminishing unwanted tendencies of highly functionalized molecules to form "structure" in solution. Even short sulfide-linked DNA analogues displayed association properties different from those displayed by standard DNA molecules. Complex formation observed with sulfide-linked tetramers by HPLC study in different solvents suggested that the complex is formed using hydrogen bonding. Sulfone-linked dinucleotides display Watson-Crick behavior; the tetramer, however, displayed self-structure. Self-structure and self-aggregation become more prominent as the length of the oligonucleotide analogues increases. The tendency to self-aggregate can be decreased by adding a charged sulfonate group to the 3'-end of the DNA analogue. Features of the second-generation model are important for many areas of nucleic acid chemistry, from the design of nucleic acid therapeutic agents to the search for life on other planets.     

Current perspectives on benzoflavone analogues with potent biological activities: A review

Medicinal chemistry investigators have isolated and synthesized benzoflavone analogues with diverse bioactivities including enzyme inhibitory activity, central nervous system (CNS) activity, anti-inflammatory activity, anti-microorganism activity, hypoglycemic activity, and receptor modulating potential. SAR (Structure-Activity Relationship) studies have been conducted extensively and plenty of benzoflavone analogues have been prepared for potential targets. Herein, we review the pharmacology properties and SAR for benzoflavone analogues, and provide a brief summarization of synthetic strategies, wishing to give perspective on the research and development of benzoflavone derivatives.