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Abstract: For zeolite-type frameworks the focus has for a long time been put on producing new structures that can give optimized properties for a variety of different purposes. Many new structures have been produced on a trial and error basis. Open-framework germanates have played the role of forming many new structures as it is easier to form certain building units within the germanate system. It is time to start comparing synthesis mechanisms and building units to determine how we can control the synthesis. Here we will give an overview of some of the structures found within the open-framework germanate system and demonstrate that in order for more optimized systems to be synthesized there is a clear need for the more detailed comparison of the structural systematics of existing materials.

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Abstract: The search for effective drug delivery systems is one of the major challenges in drug formulation especially for biopharmaceuticals Such as proteins, and peptide-based drugs and vaccines. A procedure has been developed whereby human serum albumin (HSA) call be Used as a delivery vehicle for these biomolecules using its role as main ratty acid carrier. Using essentially fatty acid free HSA (HSAff) it is possible to form stable complexes with lipidic chain compounds (lipo-compounds). Two lipo-compounds have been used to develop this system, a novel antimicrobial lipopeptide and gamma-amino-n-butyric acid, GABA. conjugated with an alkyl chain, lipo-GABA, in both cases C8 and C14 alkyl chain lengths were evaluated. The HAS-lipo compound complex had a mutual stabilizing effect on both the HSA and the lipo-compound. The protease enzyme study showed that the alkyl chains of these lipo-compounds bound to HSAff confer a similar if not greater biostability than caprylic acid shown by CD and importantly, the bound lipopeptide was stabilized by the HSA shown by mass spectrometry. Heat stability studies at 60 degrees C over 10 h also confirmed that the lipo-HSA complexes confer stability and provide a method of preparing sterile formulation for therapeutic use. No further increased in stability of the lipo-compounds when HSA containing fatty acid (HSAfa) Was used. With the antimicrobial lipopeptide, there was enhanced activity with HSAff formulation suggesting increased biostability and bioavailability of compounds. These finding allowed us to develop a simple and effective way of delivering lipo-compounds using fatty acid free HSA as the carrier.

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Abstract: Phospho-CDK2/cyclin A, a kinase that is active in cell cycle S phase, contains an RXL substrate recognition site that is over 40 Å from the catalytic site. The role of this recruitment site, which enhances substrate affinity and catalytic efficiency, has been investigated using peptides derived from the natural substrates, namely CDC6 and p107, and a bispeptide inhibitor in which the ?-phosphate of ATP is covalently attached by a linker to the CDC6 substrate peptide. X-ray studies with a 30-residue CDC6 peptide in complex with pCDK2/cyclin A showed binding of a dodecamer peptide at the recruitment site and a heptapeptide at the catalytic site, but no density for the linking 11 residues. Kinetic studies established that the CDC6 peptide had an 18-fold lower Km compared with heptapeptide substrate and that this effect required the recruitment peptide to be covalently linked to the substrate peptide. X-ray studies with the CDC6 bispeptide showed binding of the dodecamer at the recruitment site and the modified ATP in two alternative conformations at the catalytic site. The CDC6 bispeptide was a potent inhibitor competitive with both ATP and peptide substrate of pCDK2/cyclin A activity against a heptapeptide substrate (Ki = 0.83 nm) but less effective against RXL-containing substrates. We discuss how localization at the recruitment site (KD 0.4 ?m) leads to increased catalytic efficiency and the design of a potent inhibitor. The notion of a flexible linker between the sites, which must have more than a minimal number of residues, provides an explanation for recognition and discrimination against different substrates.

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Abstract: Bacteria are abundant in many natural and engineered environments where they are thought to exert important controls on the cycling, mobility, bioavailability, and toxicity of metal contaminants. In order to probe their role in moderating the behavior of lanthanides, pH-dependent adsorption edges of 13 individual lanthanides and yttrium to the Gram-negative bacterium Pantoea agglomerans were used to generate discrete site surface complexation constants. The calculated surface complexation constants were compared with stability constants estimated using linear free energy relationships based on a number of hydroxyl-containing ligands. The experimental data suggests that lanthanide adsorption edges below pH 6.5 are consistent with adsorption to phosphate groups for the light and some of the middle lanthanides (La to Gd), whereas some of the middle and heavy lanthanides appear to favor carboxyl co-ordination (Tb to Yb), although exceptions occur in each grouping. The experimentally derived surface complexation constants for carboxyl coordination were of similar magnitude to stability constants estimated from linear free energy correlations using fulvic acid stability constants. The implication is that the adsorption of lanthanides to bacterial surfaces could be modeled reasonably well using lanthanide stability constants for natural organic matter, except perhaps at low pH where phosphate binding dominates.