Cationic poly(methacryl oxyethyl trimethylammonium) and its poly(ethylene glycol)‐grafted analogue as capillary coating materials in electrophoresis

Cationic polyelectrolytes were synthesized and used as semipermanent coating materials for capillaries in electrophoresis. The polyelectrolytes used were a homopolymer of poly(methacryl oxyethyl trimethylammonium chloride) (PMOTAC) and its poly(ethylene glycol) (PEG)‐grafted analogue. Two PMOTAC polyelectrolytes, with molar masses of 85,000 and 300,000 g/mol, and PEG‐grafted PMOTAC with a molar mass of 280,000 g/mol were synthesized and then characterized by size exclusion chromatography (SEC) and nuclear magnetic resonance (NMR) spectroscopy. Attachment of the polyelectrolytes to the wall of the fused silica capillary for electrophoresis caused the electroosmotic flow (EOF) to reverse. The polyelectrolyte coatings were tested over the pH range 2–11 at different buffer ionic strengths, and the most stable and strongest anodic EOFs were obtained at acidic pH values with low ionic strength buffers. Between runs the capillary is merely rinsed for 2 or 3 min with the background electrolyte solution. With the PMOTAC coatings at pH values ≤5, the RSDs of the EOFs were less than 2.9% after 60 injections. The effects of the molar mass of the polycation and of PEGylation of PMOTAC on the interactions between the polycations and basic proteins were studied at acidic pH values. The differences in the effective electrophoretic mobilities, resolution values, and plate numbers of the proteins with the different coatings were due to the EOF, as demonstrated through calculations of reduced mobilities, relative resolution values, and relative plate numbers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 2655–2663, 2007     

Enantio- and Diastereoselective Aldol-Reaction of 2,6-Dimethylphenyl Propionate Using Titanium-Carbohydrate Complexes

Chloro(cyclopentadienyl)bis(1,2:5,6-di-O-isopropylidene-α-D -glucofuranos-3-O-yl)titanium ( 1 ) is used for the transmetallation of Li-enolates obtained from propionyl derivatives. While such Ti-enolates of ketones and hydrazones appear to be unreactive, the (E)enolate 13 of 2,6-dimethylphenyl propionate ( 11 ) adds to the re-side of aldehydes, affording various syn-aldols 14 with high dia- and enantioselectivity (92–97% ds, 91–97% ee, cf. Scheme 2 and Table 1). Racemic syn-aldols (±)- 14 are obtained analogously from the achiral bis(2-propyloxy)-Ti-enolate 15 (Scheme 2 and Table 2). In contrast to the unstable Li-enolate 10 , the Ti-enolates 13 and 15 isomerize at ?30°, presumably to the thermodynamically more stable (Z)-enolates (Scheme 4), While the diastereoselectivity of the achiral enolate 15 is lost upon this equilibration, the chiral (Z)-enolate 27 quite unexpectedly affords anti-aldols 12 of high optical purity (94–98% ec) and, in most cases, with acceptable-to-good diastereoselectivity (82–90% ds). Notable exceptions are branched unsaturated and aromatic aldehydes which form a greater proportion of synepimers of moderate optical purity (Scheme 5 and Table 3). Consistent with these findings, re-facial-and ami -selective aldol-addition is also exhibited by the (Z)-configurated Ti-enolate 22 of N-propionyl-oxazolidi-none 19 (Scheme 3).     

GnRH binding RNA and DNA Spiegelmers: a novel approach toward GnRH antagonism

Mirror-image oligonucleotide ligands (Spiegelmers) that bind to the pharmacologically relevant target gonadotropin-releasing hormone I (GnRH) with high affinity and high specificity have been identified using the Spiegelmer technology. GnRH is a decapeptide that plays an important role in mammalian reproduction and sexual maturation and is associated with several benign and malignant diseases. First, aptamers that bind to D-GnRH with dissociation constants of 50-100 nM were isolated out of RNA and DNA libraries. The respective enantiomers of the DNA and RNA aptamers were synthesized, and their binding to L-GnRH was shown. These Spiegelmers bind to L-GnRH with similar affinity to that of the corresponding aptamers that bind to D-GnRH. We further demonstrated dose-dependent inhibition of GnRH-induced Ca(2+) release in Chinese hamster ovary cells that were stably transfected with the human GnRH receptor.     

One-Bond 13C, 13C-Spin Coupling in η4-, η3- and η2-Olefin Transition Metal Complexes

One-bond ¹³C, ¹³C-spin-coupling constants have been measured, with natural isotope abundance, in η⁴-diene, η³-allyl and η²-ene transition-metal carbonyl complexes. Typical values of ¹J(C,C) are given for Fe-, Ru- and Os-complexes with the three types of olefinic ligands. The effects of substituents and the structural significance of the C,C-coupling constants are discussed.     

Fast folding and comparison of RNA secondary structures

Summary Computer codes for computation and comparison of RNA secondary structures, the Vienna RNA package, are presented, that are based on dynamic programming algorithms and aim at predictions of structures with minimum free energies as well as at computations of the equilibrium partition functions and base pairing probabilities.An efficient heuristic for the inverse folding problem of RNA is introduced. In addition we present compact and efficient programs for the comparison of RNA secondary structures based on tree editing and alignment.All computer codes are written in ANSI C. They include implementations of modified algorithms on parallel computers with distributed memory. Performance analysis carried out on an Intel Hypercube shows that parallel computing becomes gradually more and more efficient the longer the sequences are.

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Schnelle Faltung und Vergleich von Sekundärstrukturen von RNA

Zusammenfassung Die im Vienna RNA package enthaltenen Computer Programme für die Berechnung und den Vergleich von RNA Sekundärstrukturen werden präsentiert. Ihren Kern bilden Algorithmen zur Vorhersage von Strukturen minimaler Energie sowie zur Berechnung von Zustandssumme und Basenpaarungswahrscheinlichkeiten mittels dynamischer Programmierung.Ein effizienter heuristischer Algorithmus für das inverse Faltungsproblem wird vorgestellt. Darüberhinaus präsentieren wir kompakte und effiziente Programme zum Vergleich von RNA Sekundärstrukturen durch Baum-Editierung und Alignierung.Alle Programme sind in ANSI C geschrieben, darunter auch eine Implementation des Faltungs-algorithmus für Parallelrechner mit verteiltem Speicher. Wie Tests auf einem Intel Hypercube zeigen, wird das Parallelrechnen umso effizienter je länger die Sequenzen sind.

     

Helicity‐Encoded Molecular Strands: Efficient Access by the Hydrazone Route and Structural Features

Control over the folding of molecular strands may be achieved by appropriate choice of the constituting subunits, in particular for chains of specific heterocycles such as sequences of directly connected pyridine (py) and pyrimidine (pym) rings, which are known to fold into extended helical structures. Since the hydrazone (hyz) group represents an isomorphic analogue of a py site, the condensation of hydrazine and carboxaldehyde derivatives of pym offers a very efficient approach to strands incorporating hyz instead of py units and constituted by sequences of alternating hyz and pym groups. A series of such strands of different lengths, up to ten hyz units, i.e., 1 – 7 , were synthesized. Their spectral properties indicate that they fold indeed into helical shapes. Extensive characterization was performed in solution by ¹HNMR spectroscopy and in the solid state by determination of the crystal structures of eight such strands. They all display the expected helical geometry with up to 3 ¹/₃ turns and direct stacking contacts. The efficiency and flexibility of the synthetic approach as well as its wide potential for generation of diversity through lateral decoration make the (hyz? pym) subunit a particularly attractive helicity codon.     

Analysis of RNA sequence structure maps by exhaustive enumeration I. Neutral networks

Summary Global relations between RNA sequences and secondary structures are understood as mappings from sequence space into shape space. These mappings are investigated by exhaustive folding of allGC andAU sequences with chain lengths up to 30. The computed structural data are evaluated through exhaustive enumeration and used as an exact reference for testing analytical results derived from mathematical models and sampling based on statistical methods. Several new concepts of RNA sequence to secondary structure mappings are investigated, among them that ofneutral networks (being sets of sequences folding into the same structure). Exhaustive enumeration allows to test several previously suggested relations: the number of (minimum free energy) secondary structures as a function of the chain length as well as the frequency distribution of structures at constant chain length (commonly resulting in generalized forms ofZipf's law).

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Analyse der Beziehungen zwischen RNA-Sequenzen und Sekundärstrukturen durch vollständige Faltung, 1. Mitt. Faltung, Neutrale Netzwerke

Zusammenfassung Die globalen Benziehungen zwischen RNA-Sequenzen und Sekundärstrukturen werden als Abbildungen aus einem Raum aller Sequenzen in einen Raum aller Strukturen aufgefaßt. Diese Abbildungen werden durch Falten aller binären Sequenzen desGC-undAU-Alphabets mit Kettenlängen bis zun=30 untersucht. Die berechneten Strukturdaten werden durch vollständiges Abzählen ausgewertet und als eine exakte Referenz zum Überprüfen analytischer Resultate aus mathematischen Modellen sowie zum Testen statistisch erhobener Proben verwendet. Einige neuartige Konzepte zur Beschreibung der Beziehungen zwischen Sequenzen und Strukturen werden eingehend untersucht, unter ihnen der Begriff derneutralen Netzwerke. Ein neutrales Netzwerk besteht aus allen Sequenzen, die eine bestimmte Struktur ausbilden. Vollständiges Abzählen ermöglicht beispielsweise die Bestimmung aller Strukturen minimaler freier Energie in Abhängigkeit von der Kettenlänge ebenso wie die Bestimmung der Häufigkeitsverteilungen der Strukturen bei konstanten Kettenlängen. Die letzteren folgen einer verallgemeinerten FormZipfschen Gesetzes.