Synthesis and Properties of Oligodeoxynucleotide Analogs with Bis(methylene) Sulfone Bridges

A convergent, solution‐phase synthesis was developed for the bis(methylene) sulfone‐bridged oligodeoxynucleotide analogs (SNA) 5′‐d(HOCH₂‐Tso ₂Tso ₂Tso ₂Cso ₂Tso ₂Tso ₂Tso ₂T‐CH₂SO )‐3′ ( 35b ) and 5′‐d(HOCH₂‐Tso ₂Tso ₂Tso ₂Tso ₂Tso ₂Tso ₂Tso ₂T‐CH₂SO )‐3′ ( 34c ) (SO₂ corresponds to CH₂SO₂CH₂ instead of OP(?O)(O^?)(O). In these, the phosphodiester linkages are replaced by non‐ionic bis(methylene) sulfone linkers. The general strategy involved convergent coupling of 3′,5′‐bishomo‐β‐D ‐deoxyribonucleotide analogs functionalized at the 6′‐end (?CH₂? C(5′)) as bromides or mesylates and at the CH₂? C(3′) position as thiols, with the resulting thioether being oxidized to the corresponding sulfone. A single charge was introduced at the terminal CH₂? C(3′) position of the octamers to increase their solubility in water. During the synthesis, it became apparent that the key intermediates generated secondary structures through either folding or aggregation in a variety of solvents. This generated unusual reactivity and was unique for very similar structures. For example, although the dimeric thiol d(BzOCH₂‐Tso ₂C‐CH₂SH) ( 14b ) was a well‐behaved synthetic intermediate, the tetrameric thiol d(TrOCH₂‐Tso ₂Tso ₂Tso ₂^toC‐CH₂SH) derived from the corresponding thioacetate was rapidly converted to a disulfide by very small amounts of oxidant ( 28 → 29 , Scheme 6), while the analogous tetrameric thiol d(BzOCH₂‐Tso ₂Ts Tso ₂T‐CH₂SH) ( 26 ), differing only by a single heterocycle, was oxidized much more slowly (Bz=PhCO, Tr=Ph₃C, to=2‐MeC₆H₄CO (at N⁴ of dc)). The sequence‐dependent reactivity, well known in many classes of natural products (including polypeptides), is not prominent in natural oligonucleotides. These results are discussed in light of the proposal that the repeating negative charge in nucleic acids is key to their ability to serve as genetic molecules, in particular, their capability to support Darwinian evolution. The ability of 5′‐d(HOCH₂‐Tso ₂Tso ₂Tso ₂Cso ₂Tso ₂Tso ₂Tso ₂T‐CH₂SO )‐3′ ( 35b ) to bind as a third strand to duplex DNA was also examined. No triple‐helix‐forming propensity was detected in this molecule.     

Analysis of surface layers of an iron axe from Early Medieval Age

An ancient axe from Early Medieval Age which was unearthed on a territory of the archaeological excavation site near the village Borovce (Slovakia) is investigated. The surface of the axe was supposed to be covered with a sort of glassy system. Mössbauer effect measurements performed in backscattering and transmission geometry upon original as well as powdered pieces of the axe confirmed that the surface layers of the axe consist of goethite, lepidocrite, akageneite, and/or magnetite. After temperature treatment at 400°C/100 min hematite and maghemite were found; these are products of thermal decomposition of the above mentioned iron phases. These findings ruled out the hypothesis that the surface covering substance was put on the axe by intention.     

Antiprotozoal Activities of Epimeric Aminobicycles

Summary. We synthesized several 4-aminobicyclo[2.2.2] octan-2-ols and 4-amino-2-azabicyclo[3.2.2]nonanes from epimerized 4-amino-bicyclo[2.2.2]octan-2-ones. The new compounds were tested for their activity against Trypanosoma b. rhodesiense, the causative organism of East African sleeping sickness, and Plasmodium falciparum K ₁, a multiresistant protozoan parasite which causes Malaria tropica. The results are compared to the activities of their formerly synthesized stereoisomers and structure–activity relationships are discussed.     

Quantum nonintegrability and the classical limit for usp(4) systems

We investigate the transition from integrability to chaos in a system built of usp(4) elements, both in the quantum case and in its classical limit, obtained using coherent states. This algebraic Hamiltonian consists in an integrable term plus a nonlinear perturbation, and we see that the level spacing distribution for the quantum system is well approximated by the Berry-Robnik-Brody distribution, and accordingly the classical limit displays mixed dynamics.     

Iterative patching and the asymmetric traveling salesman problem

Although Branch-and-Bound (BnB) methods are among the most widely used techniques for solving hard problems, it is still a challenge to make these methods smarter. In this paper, we investigate iterative patching, a technique in which a fixed patching procedure is applied at each node of the BnB search tree for the Asymmetric Traveling Salesman Problem. Computational experiments show that iterative patching results in general in search trees that are smaller than the classical BnB trees, and that solution times are lower for usual random and sparse instances. Furthermore, it turns out that, on average, iterative patching with the Contract-or-Patch procedure of Glover, Gutin, Yeo and Zverovich (2001) and the Karp–Steele procedure are the fastest, and that ‘iterative’ Modified Karp–Steele patching generates the smallest search trees.     

Molecular origin of model membrane bending rigidity

The behavior of the bending modulus kappa of bilayers in lamellar phases was studied by Small Angle X-ray Scattering technique for various nonionic C(i)E(j) surfactants. The bilayers are either unswollen and dispersed in water or swollen by water and dispersed in dodecane. For unswollen bilayers, the values of kappa decrease with both an increase in the area per surfactant molecule and in the polar head length. They increase when the aliphatic chain length increases at constant area per surfactant molecule. Whereas for water-swollen membranes, the values of kappa decrease as the content of water increases converging to the value of the single monolayer bending modulus. Such a behavior results from the decoupling of the fluctuations of the two surfactant membrane monolayers. Our results emphasize the determinant contribution of the surfactant conformation to kappa.     

Modified phase contrast for recording of holographic optical elements

A modified phase contrast method is described for the fabrication of holographic optical elements with in-line diffraction patterns. In this method, a liquid crystal phase modulator is addressed by computer-generated holograms to achieve variable phase gratings. The phase gratings are imaged onto photosensitive material by a phase contrast method without a Fourier filter. We show the analytical treatment of the modified phase contrast method and demonstrate the application in holographic recording.     

Structure Elucidation and Activity of Kolossin A,the D‐/L‐Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase

The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D ‐/ L ‐peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness.