Synthesis of Novel Planar-Chiral Charge-Compensated -Carborane-Based Amino Acid.

Amino acids with unusual types of chirality and their derivatives have recently attracted attention as precursors in the synthesis of chiral catalysts and peptide analogues with unique properties. In this study, we have synthesized a new -carborane-based planar-chiral amino acid, in the molecule of which the amino group is directly bonded to the B(3) atom, and the carboxyl group is attached to the B(9) atom through the CHS(Me) fragment. 3-Amino-9-dimethylsulfonio--carborane, prepared in three steps from 3-amino--carborane in a high yield, was a key intermediate in the synthesis of the target planar-chiral amino acid.

Synthesis and Assessment of Antiplatelet and Antithrombotic Activity of 4-Amino-Substituted 5-Oxoproline Amides and Peptides.

Venous thromboembolism is a serious problem because it significantly increases the risk of developing vascular complications in elderly patients with obesity or immobilization, cancer, and many other diseases. Thus, there is a need to study new therapeutic strategies, including new medicinal agents for the efficient and safe correction of thrombus disorders. In this work, we have synthesized a number of new amides and peptides of 4-amino-5-oxoprolines and studied their antiplatelet and antithrombotic activity in experiments in vitro and in vivo.

Large Subunit of the Human Herpes Simplex Virus Terminase as a Promising Target in Design of Anti-Herpesvirus Agents.

Herpes simplex virus type 1 (HSV-1) is an extremely widespread pathogen characterized by recurrent infections. HSV-1 most commonly causes painful blisters or sores around the mouth or on the genitals, but it can also cause keratitis or, rarely, encephalitis. First-line and second-line antiviral drugs used to treat HSV infections, acyclovir and related compounds, as well as foscarnet and cidofovir, selectively inhibit herpesvirus DNA polymerase (DNA-pol).

Darwin, Haeckel, and the "Mikluskan gas organ theory".

A previously unknown reference to the Russian ethnologist, biologist, and traveler Nikolai N. Miklucho-Maclay (1846-1888) was discovered in correspondence between Charles Darwin (1809-1882) and Ernst Haeckel (1834-1919). This reference has remained unknown to science, even to Miklucho-Maclay's biographers, probably because Darwin used the Russian nickname "Mikluska" when alluding to this young scientist.

Synthesis of Charge-Compensated -Carboranyl Derivatives of Sulfur-Containing Amino Acids and Biotin.

A new group of charge-compensated -carboranyl derivatives of sulfur-containing amino acids and biotin has been synthesized in which the boron atom in position 9 or 10 of carborane is attached to a positively charged sulfur atom. The possibilities of obtaining symmetrical B(10)-substituted and asymmetric B(9)-substituted -carboranes were studied. Using the example of ()-methionine and D-biotin derivatives, water-soluble S-substituted charge-compensated -carboranes with free functional groups were prepared.

Synthesis of Novel Carborane-Containing Derivatives of RGD Peptide.

Short peptides containing the Arg-Gly-Asp (RGD) fragment can selectively bind to integrins on the surface of tumor cells and are attractive transport molecules for the targeted delivery of therapeutic and diagnostic agents to tumors (for example, glioblastoma). We have demonstrated the possibility of obtaining the - and -protected RGD peptide containing 3-amino--carborane and a glutaric acid residue as a linker fragment. The resulting carboranyl derivatives of the protected RGD peptide are of interest as starting compounds in the synthesis of unprotected or selectively protected peptides, as well as building blocks for preparation of boron-containing derivatives of the RGD peptide of a more complex structure.

Carborane-Containing Folic Acid -Amides: Synthesis and In Vitro Evaluation of Novel Promising Agents for Boron Delivery to Tumour Cells.

The design of highly selective low-toxic, low-molecular weight agents for boron delivery to tumour cells is of decisive importance for the development of boron neutron capture therapy (BNCT), a modern efficient combined method for cancer treatment. In this work, we developed a simple method for the preparation of new - and -carborane-containing folic acid -amides containing 18-20 boron atoms per molecule. Folic acid derivatives containing -carborane residues were characterised by high water solubility, low cytotoxicity, and demonstrated a good ability to deliver boron to tumour cells in in vitro experiments (up to 7.

Effect of the Silica-Magnetite Nanocomposite Coating Functionalization on the Doxorubicin Sorption/Desorption.

A series of new composite materials based on FeO magnetic nanoparticles coated with SiO (or aminated SiO) were synthesized. It has been shown that the use of -(phosphonomethyl)iminodiacetic acid (PMIDA) to stabilize nanoparticles before silanization ensures the increased content of a SiO phase in the FeO@SiO nanocomposites (NCs) in comparison with materials obtained under similar conditions, but without PMIDA. It has been demonstrated for the first time that the presence of PMIDA on the surface of NCs increases the level of Dox loading due to specific binding, while surface modification with 3-aminopropylsilane, on the contrary, significantly reduces the sorption capacity of materials.

Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2-[1,4]benzoxazine and Evaluation of Their Antiviral Activity.

A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2-[1,4]benzoxazine and its ()-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were confirmed by H, F, and C NMR spectral data. Enantiomeric purity of optically active derivatives was confirmed by chiral HPLC.

-Aminoacyl-3-amino--carboranes as a Group of Boron-Containing Derivatives of Natural Amino Acids.

A new group of -carboranyl derivatives of natural ()-amino acids containing from 9 to 18 boron atoms was obtained in good yields as a result of acylation of 3-amino-1,2-dicarba--dodecaborane followed by deboronation. The proposed approach is convenient and based on the use of readily available reagents and is suitable for the synthesis of enantiopure -carboranyl derivatives of amino acids with various side chains, including water-soluble boron-containing amino acids (17 examples).

Acylative kinetic resolution of racemic methyl-substituted cyclic alkylamines with 2,5-dioxopyrrolidin-1-yl ()-2-phenoxypropanoate.

The diastereoselective acylation of a number of racemic methyl-substituted cyclic alkylamines with active esters of 2-phenoxypropanoic acid was studied in detail. The ester of ()-2-phenoxypropanoic acid and -hydroxysuccinimide was found to be the most selective agent. The highest stereoselectivity was observed in the kinetic resolution of racemic 2-methylpiperidine in toluene at -40 °C (selectivity factor = 73) with the predominant formation of (,)-amide (93.

The biogenetic law and the Gastraea theory: From Ernst Haeckel's discoveries to contemporary views.

More than 150 years ago, in 1866, Ernst Haeckel published a book in two volumes called Generelle Morphologie der Organismen (General Morphology of Organisms) in the first volume of which he formulated his biogenetic law, famously stating that ontogeny recapitulates phylogeny. Here, we describe Haeckel's original idea as first formulated in the Generelle Morphologie der Organismen and later further developed in other publications until the present situation in which molecular data are used to test the "hourglass model," which can be seen as a modern version of the biogenetic law. We also tell the story about his discovery, while traveling in Norway, of an unknown organism, Magosphaera planula, that was important in that it helped to precipitate his ideas into what was to become the Gastraea theory.

Stereochemical aspects in the synthesis of novel N-(purin-6-yl)dipeptides as potential antimycobacterial agents.

The synthesis of purine conjugates with natural amino acids is one of the promising directions in search for novel therapeutic agents, including antimycobacterial agents. The purpose of this study was to synthesize N-(purin-6-yl)dipeptides containing the terminal fragment of (S)-glutamic acid. To obtain the target compounds, two synthetic routes were tested.

[Antiviral effect of novel purine conjugate LAS-131 against Herpes simplex virus type 1 (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1) in vitro].

Introduction: Herpes simplex viruses type 1 (HSV-1) are extremely widespread throughout the world and, similar to other herpesviruses, establish lifelong persistent infection in the host. Reactivating sporadically, HSV-1 elicits recurrences in both immunocompetent and immunocompromised individuals and can cause serious diseases (blindness, encephalitis, generalized infections). The currently available antiherpetic drugs that aimed mainly at suppressing replication of viral DNA are not always effective enough, for example, due to the development of drug resistance.

Ernst Haeckel, Nikolai Miklucho-Maclay and the racial controversy over the Papuans.

Background: The "German Darwin" Ernst Haeckel (1834-1919) was a key figure during the first "Darwinian revolution", a time when the foundations of the modern evolutionary theory were laid. It was Haeckel, who crucially contributed to the visualization of the Darwinian theory by designing "genealogical-trees" illustrating the evolution of various species, including humans. Although the idea of explaining human evolution by natural selection belongs to Darwin, Haeckel was the first who attempted to create a new exact anthropology based on the Darwinian method.

Ernst Haeckel in the history of biology.

The German zoologist Ernst Haeckel (1834-1919) was arguably the most influential champion of Darwin's theory of evolution on the European continent and one of the most significant worldwide. As his biographer Robert Richards emphasized: "More people at the turn of the century learned of evolutionary theory from his pen than from any other source, including Darwin's own writings" [1]. Furthermore, Darwin himself considered Haeckel a crucial proponent of his theory.

Ecology and Evolution: Haeckel's Darwinian Paradigm.

Ernst Haeckel coined the term ecology in the process of Darwinizing our understanding of nature. His concept of ecology was part of a theoretical system embracing development, evolution, and environment. We outline Haeckel's views on ecology as an evolutionary science and demonstrate their importance for current theoretical developments.

Ernst Haeckel's contribution to Evo-Devo and scientific debate: a re-evaluation of Haeckel's controversial illustrations in US textbooks in response to creationist accusations.

As Blackwell (Am Biol Teach 69:135-136, 2007) pointed out, multiple authors have attempted to discredit Haeckel, stating that modern embryological studies have shown that Haeckel's drawings are stylized or embellished. More importantly, though, it has been shown that the discussion within the scientific community concerning Haeckel's drawings and the question of whether embryonic similarities are convergent or conserved have been extrapolated outside the science community in an attempt to discredit Darwin and evolutionary theory in general (Behe in Science 281:347-351, 1998; Blackwell in Am Biol Teach 69:135-136, 2007; Pickett et al. in Am Biol Teach 67:275, 2005; Wells in Am Biol Teach 61:345-349, 1999; Icons of evolution: science or myth? Why much of what we teach about evolution is wrong.

Evolutionary ethics and Haeckelian monism: the case of Heinrich Schmidt's Harmonie (1931).

This paper offers the first ever published discussion of the ethical treatise Harmonie: Versuch einer monistischen Ethik [Harmony: an attempt at a monistic ethics] by Heinrich Schmidt (1874-1935), one of the leading figures in the circle of Ernst Haeckel. Published near the end of Schmidt's life (1931), it constituted a kind of summation of decades of intense involvement in the "project" of German monism that found its epicentre in Jena, and in Haeckel's attempts at founding it on Darwinian and Goethian lines. After a brief description of Schmidt's life and works, we summarize the main lines of Haeckel's evolutionary thought and their expression in his sparse ethical writings.

The reception of Haeckel in pre-revolutionary Russia and his impact on evolutionary theory.

The "German Darwin" Ernst Haeckel was influential not only in Germany, but in non-German-speaking countries as well. Due to the widespread use of German as a language of science in the Russian Empire along with growing Russian-German links in various scientific fields, Haeckel directly and indirectly influenced Russian intellectual landscape. The objective of the present paper is to investigate Haeckel's impact on Russian biology before the Bolshevik Revolution of 1917.

Ernst Haeckel's embryology in biology textbooks in the German Democratic Republic, 1951-1988.

In our era of computers and computer models, the importance of physical or graphical models for both research and education in developmental biology (embryology) is often forgotten or at least underappreciated. Still, one important aspect of embryology is the (evolutionary) developmental anatomy of both human and animal embryos. Here, we present a short history of the visualization of Ernst Haeckel's "biogenetic law" and his "gastraea theory" in biology textbooks from the German Democratic Republic (GDR) between 1951 and 1988.