Peptide phage display as a tool for drug discovery: targeting membrane receptors

Ligands selected from phage-displayed random peptide libraries tend to be directed to biologically relevant sites on the surface of the target protein. Consequently, peptides derived from library screenings often modulate the target protein's activity in vitro and in vivo and can be used as lead compounds in drug design and as alternatives to antibodies for target validation in both genomics and drug discovery. This review discusses the use of phage display to identify membrane receptor modulators with agonistic or antagonistic activities. Because isolating or producing recombinant membrane proteins for use as target molecules in library screening is often impossible, innovative selection strategies such as panning against whole cells or tissues, recombinant receptor ectodomains, or neutralizing antibodies to endogenous binding partners were devised. Prominent examples from a two-decade history of peptide phage display will be presented, focusing on the design of affinity selection experiments, methods for improving the initial hits, and applications of the identified peptides.     

Note on list star edge-coloring of subcubic graphs

A star edge-coloring of a graph is a proper edge-coloring without bichromatic paths and cycles of length four. In this paper, we consider the list version of this coloring and prove that the list star chromatic index of every subcubic graph is at most 7, answering the question of Dvořák et al (J Graph Theory, 72 (2013), 313-326).     

Partitioning of natural radionuclides in sediments around a former uranium mine and mill

Partitioning of natural radionuclides in sediments from streams affected by the waste piles of the former uranium mine and mill located at ?irovski vrh, Slovenia, was performed by applying a sequential extraction procedure. The sediments were collected at three sites located upstream and three sites located downstream of the waste piles. Then the four-step Community Bureau of Reference (BCR) sequential extraction protocol was applied to the samples and the natural radionuclides ²³⁸U, ²³⁰Th, ²²⁶Ra, ²¹⁰Pb and ²¹⁰Po were analysed in each extraction fraction. It was expected that the fractionation of natural radionuclides originating from the waste piles would differ from that upstream of the influence of waste piles because their chemical environment had been altered during the processes of uranium extraction. This difference could allow tracing of the radionuclides coming from the waste piles downstream of the affected watercourses. The results definitely showed that the total activity concentrations at sites downstream of the influence of the waste piles were higher than at sites upstream of the piles. However, this difference was geographically very limited and could no longer be detected already at a distance of about 5 km downstream. Unexpectedly, the fractionation of radionuclides upstream and downstream of the area of influence of the waste piles did not appear to be significantly altered. The sole differences found were for ²³⁸U and ²²⁶Ra in the second fraction (the “Fe/Mn oxides” fraction) and for ²¹⁰Po in the fourth fraction (the “residue” fraction) of the BCR sequential extraction protocol.     

Acoustic emission of a crazing polymer

The acoustic emission from a crazing polyvinyltoluene in a tensile and bending experiment is described. Acoustic emission appears as a series of bursts which most likely correspond to the initiation and growth of crazes. The emission intensity is characterised by acoustic activity (pulse rate) measured by the ring-down technique. The average activity increases with strain. During repeated loading the acoustic activity shows a measurable intensity and significant rise only beyond the maximum strain of the former runs. This is equivalent to Kaiser's effect in metals. Acoustic emission during the creep experiment occurs in three characteristic periods. They are characterized as the relaxation, fatigue, and breakdown periods. Visual observations indicate that the relaxation period corresponds to the initiation, and the fatigue period to the growth of crazes. In the breakdown period a macroscopic crack develops and the sample fails.     

Plastic deformation of polyethylene. I. Change of morphology during drawing of polyethylene of high density

The transformation of microspherulitic quenched and annealed polyethylene film into highly oriented drawn material with the characteristic fiber structure was investigated by small-angle and wide-angle x-ray measurements and by a study of the thermograms after the fuming nitric acid treatment. With the details of deformation depending slightly on the crystallinity, one observes generally a preferential tilt of the platelets against draw direction at draw ratios below 2. At least in annealed material, an increasing tilt of the molecule within the lamella is also observed, which leads at higher draw ratios to slipping of blocks in the crystallites. With further drawing a new fiber structure appears, which is practically independent of the thermal history of the original film. This fact is established by investigation of the crystal thickness by three different methods; investigations of small-angle scattering, study of the width of the (002) reflection, and investigation of the debris after treatment with fuming nitric acid.     

Molecular model of internal viscosity

Summary Intrinsic viscosity measurement in highly viscous solvents at high frequency of the shear flow have demonstrated the molecular weight independence of limiting intrinsic viscosity and the constancy of the ratio of internal and solvent viscosity. The former fact proves the adequacy of the formulation of the internal viscosity concept in the normal coordinate space. The latter observation requires the introduction in the molecular model of a new term derived from the excess displacement of chain elements inherent to any deformation of the necklace. As a consequence of conformational limitations by the valency angles and rotational potential energy any deformation of the necklace as described by the displacement of the beads requires displacement of some elements of the real chain in a direction perpendicular to the deformation considered. The resulting frictional forces proportional to the viscosity of the solvent are not included in the frictional coefficient of the beads and hence have to be considered separately as a contribution to internal viscosity.

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Zusammenfassung Messungen desStaudingerschen Viskositätsindex in hochviskosen Lösungsmitteln im hochfrequenten Schergefälle haben die Unabhängigkeit des Grenzindex vom Molekulargewicht und die Konstanz des Verhältnisses zwischen der Innen- und Lösungsmittelviskosität erwiesen. Nach dem ersten Befund erweist sich die Formulierung der Innenviskosität im Normalkoordinatenraum als ausreichend. Das zweite Ergebnis verlangt die Einführung eines neuen Termes in der Innenviskosität, der von der Überschußverschiebung der Kettenelemente herrührt. Als Folge der Konformationseinschränkung durch die Valenzwinkel und Rotationspotentialenergie verlangt eine jede Deformation des Perlschnurmodels, wie sie durch die Perlverschiebung beschrieben wird, die Verschiebung von einigen Gliedern der wirklichen Molekülkette in einer dazu senkrechten Richtung. Die sich daraus ergebenden zusätzlichen Reibungskräfte sind proportional der Lösungsmittelviskosität. Sie sind jedoch nicht in dem Reibungskoeffizienten der Perlen einbegriffen und müssen deshalb gesondert als Beitrag zur Innenviskosität erfaßt werden.

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With 4 figures and 1 table