A weight-function approach for determining watershed initial conditions for combustion waves

In many generic combustion models, one finds that a combustionwave will develop with a specific wave speed. However, thereare possible initial temperature profiles which do not evolveinto such waves, but rather die out to the ambient temperature.There can exist, in some models, a clear distinction betweenthose initial conditions that do evolve into combustion wavesand those that do not; this is sometimes referred to as thewatershed initial condition. When fuel consumption is consideredto be negligible, analytical methods can be used to obtain theexact watershed. In this paper, we consider the problem of determiningpseudo-watersheds and ascertaining the relationship betweenthese pseudo-watersheds and the exact watersheds. In the processa novel weight-function approach for infinite spatial domainsis developed.     

A chameleonic macrocyclic peptide with drug delivery applications

Head-to-tail cyclized peptides are intriguing natural products with unusual properties. The PawS-Derived Peptides (PDPs) are ribosomally synthesized as part of precursors for seed storage albumins in species of the daisy family, and are post-translationally excised and cyclized during proteolytic processing. Here we report a PDP twice the typical size and with two disulfide bonds, identified from seeds of Zinnia elegans. In water, synthetic PDP-23 forms a unique dimeric structure in which two monomers containing two β-hairpins cross-clasp and enclose a hydrophobic core, creating a square prism. This dimer can be split by addition of micelles or organic solvent and in monomeric form PDP-23 adopts open or closed V-shapes, exposing different levels of hydrophobicity dependent on conditions. This chameleonic character is unusual for disulfide-rich peptides and engenders PDP-23 with potential for cell delivery and accessing novel targets. We demonstrate this by conjugating a rhodamine dye to PDP-23, creating a stable, cell-penetrating inhibitor of the P-glycoprotein drug efflux pump.

The cyclic peptide PDP-23 adopts a different structure depending on conditions. In water it forms a dimer, but can unfold allowing its hydrophobic core to interact with membranes. PDP-23 shows promise as a cell penetrating scaffold for drug delivery.     

Synthesis of cytotoxic cyanobactin,Wewakazole B

We report herein the synthesis of cytotoxic cyanobactin, Wewakazole B through an efficient solution-phase approach. The key steps of the synthesis are the macrocyclic lactamization of linear dodecapeptide and construction of two hexapeptides with three different substituted oxazole rings.     

Fast cleavage kinetics of a natural hammerhead ribozyme

The hammerhead ribozyme is a small RNA motif that catalyzes the cleavage and ligation of RNA. The well-studied minimal hammerhead motif is inactive under physiological conditions and requires high Mg(2+) concentrations for efficient cleavage. In contrast, natural hammerheads are active under physiological conditions and contain motifs outside the catalytic core that lower the requirement for Mg(2+). Single-turnover kinetics were used here to characterize the Mg(2+) and pH dependence for cleavage of a trans-cleaving construct of the Schistosoma mansoni natural hammerhead ribozyme. Compared to the minimal hammerhead motif, the natural Schistosoma ribozyme requires 100-fold less Mg(2+) to achieve a cleavage rate of 1 min(-1). The improved catalysis results from tertiary interactions between loops in stems I and II and likely arises from increasing the population of the active conformation. Under optimum pH and Mg(2+) conditions this ribozyme cleaves at over 870 min(-1) at 25 degrees C, further demonstrating the impressive catalytic power of this ribozyme.