The roles of the A- and B-chains of human relaxin-2 and -3 on their biological activity

Two members of the human insulin/relaxin superfamily, relaxins-2 and 3 (H2 and H3 respectively), are separated by nearly 75 years in terms of chronological identification but are both the subject of intense recent biological study. The physiological effects of H2 relaxin include vasodilatory, anti-inflammatory, extracellular matrix remodeling, and angiogenic and anti-ischemic. Because of its potent systemic and renal vasodilatory effects, it is currently undergoing phase III clinical trial for the treatment of acute heart failure. In contrast, H3 relaxin is a highly conserved neuropeptide that has rapidly emerged as an important regulator of homeostatic physiology and complex behaviors. Because of their immense clinical potential, an understanding of the structural features that control their functions is critical for rational drug design and development. The native receptor for H2 relaxin is RXFP1. It also strongly binds to the related receptor, RXFP2. The native receptor for H3 relaxin is the unrelated receptor, RXFP3; however, it also has high affinity for another related receptor, RXFP4. Interestingly, H3 relaxin also has a high affinity for RXFP1 and can interact with RXFP2 with a significantly lower affinity. H3 relaxin thus interacts with all four of the relaxin family receptors. Previous studies have shown that H2 and H3 relaxins interact with their receptors primarily using their B-chain specific residues. However, more recent studies suggest that the role of the respective A and B chains for their activity is both peptide- and receptor-dependent. This mini-review summarizes these recent findings on the structure-activity relationships of H2 and H3 relaxins.     

Extension of the Arruda-Boyce model to the modelling of the curing process of polymers

A phenomenologically motivated finite strain general framework to simulate the curing of polymer have been developed and discussed in our recently published papers [2,4]. The Arruda-Boyce model is a classical hyperelastic model for polymeric materials. This contribution presents an extension of the Arruda-Boyce model towards modelling the curing process of polymers following our previous framework. In this paper, we will show how to model the elastic behaviour and shrinkage effects of the polymer curing process in the isothermal case using the Arruda-Boyce model. Several numerical examples have been demonstrated to verify our newly proposed modified approach in case of curing process. (© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Kinetic appearance of first-order gas-liquid expanded and liquid expanded-liquid condensed phase transitions below the triple point

Phase diagram of Gibbs monolayers of mixtures containing n-hexadecyl phosphate (n-HDP) and L-arginine (L-arg) at a molar ratio of 1:2 has been constructed by measuring surface-pressure-time (pi-t) isotherms with film balance and by observing monolayer morphology with Brewster angle microscopy (BAM). This phase diagram shows a triple point for gas (G), liquid expanded (LE), and liquid condensed (LC) phases at around 6.7 degrees C. Above this triple point, a first-order G-LE phase transition occurring at 0 surface pressure is followed by another first-order LE-LC phase transition taking place at a certain higher surface pressure that depends upon temperature. The BAM observation supports these results. Below the triple point, the pi-t measurements show only one first-order phase transition that should be G-LC. All of these findings are in agreement with the general phase diagram of the spread monolayers. However, the BAM observation at a temperature below the triple point shows that the thermodynamically allowed G-LC phase transition is, in fact, a combination of the G-LE and LE-LC phase transitions. The latter two-phase transitions are separated by time and not by the surface pressure, indicating that the G-LC phase transition is kinetically separated into these two-phase transitions. The position of the LE phase below the triple point in the phase diagram is along the phase boundary between the G and LC phases.     

Synthesis of functionalized benzylsilanes from arylzinc compounds and (iodomethyl)trimethylsilane by means of a novel Rh catalysis

[reaction: see text] The catalytic activity of a Rh complex in cross-coupling between ArZnI and TMSCH2I was examined in which the Rh complex, generated in situ from [RhCl(1,5-cyclooctadiene)]2 and 1,1'-bis(diphenylphosphino)ferrocene, exhibited excellent catalytic activity for the production of various functionalized benzylsilanes in good yields. From 31P NMR studies of various solutions containing several of the reaction components, confirmation of the rapid and quantitative transfer of aryl groups from ArZnI to the Rh complex to form arylrhodium species was ascertained. A catalytic cycle, commencing with the transmetalation, was thus proposed for the reaction.     

Microwave-assisted regioselective synthesis of natural 6-prenylpolyhydroxyisoflavones and their hydrates with hypervalent iodine reagents

Microwave-assisted oxidative rearrangement of 3′-iodotetraalkoxychalcones with hypervalent iodine such as [hydroxy(tosyloxy)iodo]benzene or [bis(trifluoroacetoxy)iodo]benzene, followed by microwave-mediated hydrolysis and in situ cyclization of the resultant acetals gave 6-iodotrialkoxyisoflavones. Pd(0)-catalyzed coupling reaction of the 6-iodoisoflavones with 2-methyl-3-butyn-2-ol under microwave irradiation gave 6-alkynylisoflavones, whose hydrogenation gave the respective hydrates of wighteone, lupisoflavone and derrubone. Wighteone (1a), lupisoflavone (1b) and derrubone (1c) were obtained by dehydration of their respective hydrates under microwave irradiation.     

Analysis of major and trace elements by INAA to predict the thousands year old sediment deposition environment in the Meghna river delta

Major, trace and rare earth elements have been measured in sediments of different layers to determine the controls of constituent minerals on the distribution of elements and sediment deposition environment in the Meghna river delta. The geochemical composition of sediments was enriched in SiO₂, Ca, Mg and Ba and depleted in Al, Fe, Ti, Mn, and Sr relative to PAAS (Post-Archaen Average Shale) value. The X-ray diffraction and elemental analyses demonstrate the dominant presence of quartz, micas, feldspar, chlorite, amphibole and clay minerals in sediments. The very low contents of trace elements suggest that the oxic condition was more prevalent during sediment deposition of Pleistocene-Holocene period and reflect the massive chemical weathering by biogeochemical reactions. The enrichment of light rare earth elements and La/Yb ratio reflect the intense silicate weathering of crustal materials and the high sediment depositional rate in the Meghna river delta.     

Synthesis of C15-C27 segment of venturicidine X by utilizing desymmetrization protocol

We have achieved the synthesis of C15-C27 fragment of venturicidine X using desymmetrization protocol, substrate-controlled Grignard reaction, Barton-McCombie reaction, Sharpless epoxidation, and TBSOTf-mediated rearrangement to produce the aldol product through a non-aldol route as the key step following 23 longest linear sequences with 6.4% overall yield starting from a known intermediate 11.     

Effect of ring fusion stereochemistry on double bond geometry. Unexpected formation of nine-membered cyclic ether with E-configurated double bond through RCM

Formation of a nine-membered cyclic ether with E-configurated double bond was observed during construction of 5-9-5 tricycles through RCM of dienes. Ring fusion stereochemistry in the products oxonenes was found to have profound influence on the olefin geometry. cis-anti-cis 5-9-5 tricycle was obtained with Z-configurated olefin while cis-syn-cis 5-9-5 system was obtained with E- as well as Z-configurated double bond with the former predominating.     

An efficient microwave-assisted synthesis of dihydropyrazinones and bis-benzoylketones

Microwave-assisted modified Sandmeyer reactions of oximinoacetanilides, themselves obtained from substituted primary aromatic amines, in concentrated H₂SO₄ give isatins. N-Acetylisatins undergo ring cleavage and subsequent ring closing with alkanediamines in the presence of ethanol under MW irradiation to give the corresponding dihydropyrazinones in excellent yields. Modification of the reaction conditions affords bis-benzoylketones under MW irradiation.