Kasstasin: A novel potent vasoconstrictor peptide from the skin secretion of the African red-legged running frog, Kassina maculata

Amphibian skin secretions are established sources of bioactive peptides. Here we describe the isolation, structural and pharmacological characterisation of a novel vasoconstrictor peptide from the skin secretion of the African hyperoliid frog, Kassina maculata, which exhibits no structural similarity to any known class of amphibian skin peptide. The peptide consists of 21 amino acid residues, FIKELLPHLSGIIDSVANAIK, and is C-terminally amidated. The provisional structure was obtained by MS/MS fragmentation using an Orbitrap mass spectrometer and L/I ambiguities were resolved following molecular cloning of biosynthetic precursor-encoding cDNA. A synthetic replicate of the peptide was found to possess weak antimicrobial and haemolytic activities but was exceptionally effective in constricting the smooth muscle of rat tail artery (EC50 of 25pM). In reflection of its exceptional potency in constricting rat arterial smooth muscle, the peptide was named kasstasin, a derivation of Kassina and “stasis” (stoppage of flow). These data illustrate the continuing potential of amphibian skin secretions to provide novel natural peptide templates for biological evaluation.

A revised structure for alkaloid 235C isolated from skin extracts of mantellid (Mantella) frogs of Madagascar

Madagascan frogs of the mantellid genus Mantella have been a rich source of alkaloids derived from dietary arthropods. Two species of frogs, inhabiting swamp forest, contain a unique set of alkaloids, previously proposed, based only on GC-MS and GC-FTIR data, to represent dehydro analogues of the homopumiliotoxins. The major alkaloid of this set, alkaloid 235C (2), now has been isolated in sufficient quantities (ca. 0.3 mg) to allow determination of the structure by NMR analysis. The structure of alkaloid 235C proved to be a 7,8-dehydro-8-desmethylpumiliotoxin. A comparison is presented between the mass, infrared, and H-1 NMR spectra of 235C (2) and a synthetic dehydrohomopumiliotoxin (1), initially proposed incorrectly as the structure for 235C.

Examination of the Silver Colloid Binding Behavior of Disulfide-Tethered Bipyridine Ligands and Their fac-Tricarbonylrhenium(I) Complexes

The syntheses of 2,2'-bipyridin-5-ylmethyl-5-(1,2-dithiolan-3-yl)pentanoate (L1) and N-(2,2'-bipyridin-5-ylmethyl)-5-(1,2-dithiolan-3-yl)pentanamide (L2) and their neutral fac carbonylrhenium(I) complexes [Re(L1)(CO)(3)Br] and [Re(L2)(CO)(3)Br] are reported. The. electronic absorption and emission spectra of the complexes are similar to the spectrum of the reference compound [Re(bipy)(CO)(3)Br] and correlate well with the density functional theory calculations undertaken. The surface-enhanced Raman spectroscopy (SERS) spectra (excited at both 532 and 785 nm) of the ligands and complexes were examined and compared to the spectrum of ethyl 5-(1,2-dithiolan-3-yl)pentanoate (L3), revealing that there is very little contribution to the spectra of these species from the dithiolated alkyl chains. The spectra are dominated by the characteristic peaks of a metalated 2,2'-bipyridyl group,arising from the silver colloid/ion complexation, and the rhenium center. The rhenium complexes show weak SERS bands related to the CO stretches and a broad band at 510 cm(-1) assigned to Re-CO stretching. Concentration dependent studies, measured by the relative intensity of several assigned peaks, indicate that, as the surface coverage increases, the bipyridine moiety lifts off the surface In the case of L1 and L2, this gives rise to complexes with silver at low concentration, enhancing the signals observed, while for the tricarbonylbromorhenium complexes of these ligands, the presence of the disulfide tether allows an enhancement in the limits of detection of these surface-borne species of 20 times in the case of [ReL2(CO)(3)Br] over [Re(bipy)(CO)(3)Br].

Forensic examination of multilayer white paint by lateral scanning Raman spectroscopy

Multilayer samples of white architectural paint potentially have very high evidential value in forensic casework, because the probability that two unrelated samples will have the same sequence of layers is extremely low. However, discrimination between the different layers using optical microscopy is often difficult or impossible. Here, lateral scanning Raman spectroscopy has been used to chemically map the cross-sections of multilayer white paint chips. It was found that the spectra did allow the different layers to be delineated on the basis of their spectral features. The boundaries between different layers were not as sharp as expected, with transitions occurring over length scales of > 20 µm, even with laser spot diameters <4 µm. However, the blurring of the boundaries was not so large as to prevent recording and identification of spectra from each of the layers in the samples. This method clearly provides excellent discrimination between different multilayer white paint samples and can readily be incorporated into existing procedures for examination of paint transfer evidence.

Examination of the physical state of chlorhexidine within viscoelastic, bioadhesive semisolids using Raman spectroscopy

This study examined the effects of polymeric components on the physical state of chlorhexidine within bioadhesive, semisolid formulations using Raman spectroscopy. Semisolid formulations were prepared in which chlorhexidine base (CHX, 5%w/w, particle size

A New Model for Automated Examination Timetabling

Automated examination timetabling has been addressed by a wide variety of methodologies and techniques over the last ten years or so. Many of the methods in this broad range of approaches have been evaluated on a collection of benchmark instances provided at the University of Toronto in 1996. Whilst the existence of these datasets has provided an invaluable resource for research into examination timetabling, the instances have significant limitations in terms of their relevance to real-world examination timetabling in modern universities. This paper presents a detailed model which draws upon experiences of implementing examination timetabling systems in universities in Europe, Australasia and America. This model represents the problem that was presented in the 2nd International Timetabling Competition (ITC2007). In presenting this detailed new model, this paper describes the examination timetabling track introduced as part of the competition. In addition to the model, the datasets used in the competition are also based on current real-world instances introduced by EventMAP Limited. It is hoped that the interest generated as part of the competition will lead to the development, investigation and application of a host of novel and exciting techniques to address this important real-world search domain. Moreover, the motivating goal of this paper is to close the currently existing gap between theory and practice in examination timetabling by presenting the research community with a rigorous model which represents the complexity of the real-world situation. In this paper we describe the model and its motivations, followed by a full formal definition.