FRAP analysis of peptide diffusion in extracellular matrix mimetic hydrogels as an in vitro model for subcutaneous injection.

Subcutaneous (SC) injection is a common route of administration for drug compounds with poor oral bioavailability. However, bioavailability is often variable and incomplete, and there is as yet no standard accepted medium for simulation of the human SC environment. In this work we evaluate a FRAP based method for quantitative determination of local self-diffusion coefficients within extracellular matrix (ECM) mimetic hydrogels, potentially useful as in vitro models for drug transport in the ECM after SC injection.

Modulating protein unfolding and refolding via the synergistic association of an anionic and a nonionic surfactant.

Hypothesis: Nonionic surfactants can counter the deleterious effect that anionic surfactants have on proteins, where the folded states are retrieved from a previously unfolded state. However, further studies are required to refine our understanding of the underlying mechanism of the refolding process. While interactions between nonionic surfactants and tightly folded proteins are not anticipated, we hypothesized that intermediate stages of surfactant-induced unfolding could define new interaction mechanisms by which nonionic surfactants can further alter protein conformation.

Investigating thermally induced aggregation of Somatropin- new insights using orthogonal techniques.

Three orthogonal techniques were used to provide new insights into thermally induced aggregation of the therapeutic protein Somatropin at pH 5.8 and 7.0.

Aggregation Behavior of Structurally Similar Therapeutic Peptides Investigated by H NMR and All-Atom Molecular Dynamics Simulations.

Understanding of peptide aggregation propensity is an important aspect in pharmaceutical development of peptide drugs. In this work, methodologies based on all-atom molecular dynamics (AA-MD) simulations and H NMR (in neat HO) were evaluated as tools for identification and investigation of peptide aggregation. A series of structurally similar, pharmaceutically relevant peptides with known differences in aggregation behavior (D-Phe-GnRH, ozarelix, cetrorelix, and degarelix) were investigated.

An integrative toolbox to unlock the structure and dynamics of protein-surfactant complexes.

The interactions between protein and surfactants play an important role in the stability and performance of formulated products. Due to the high complexity of such interactions, multi-technique approaches are required to study these systems. Here, an integrative approach is used to investigate the various interactions in a model system composed of human growth hormone and sodium dodecyl sulfate.

Manipulating Aggregation Behavior of the Uncharged Peptide Carbetocin.

Peptides are usually administered through subcutaneous injection. For low potency drugs, this may require high concentration formulations increasing the risk of peptide aggregation, especially for compounds without any intrinsic chargeable groups. Carbetocin was used as a model to study the behavior of uncharged peptides at high concentrations.

Circulation and antigenic drift in human influenza B viruses in SE Asia and Oceania since 2000.

During annual influenza epidemics, influenza B viruses frequently co-circulate with influenza A viruses and in some years, such as 2005, large outbreaks have occurred while in other years, the virus virtually disappears. Since 1987 there have been two lineages of influenza B viruses co-circulating in various countries and causing disease in humans. The proportions of these two lineages vary from year to year and country to country.

Interactions between charged polypeptides and nonionic surfactants.

The influence of molecular characteristics on the mutual interaction between peptides and nonionic surfactants has been investigated by studying the effects of surfactants on amphiphilic, random copolymers of alpha-L-amino acids containing lysine residues as the hydrophilic parts. The hydrophobic residues were either phenylalanine or tyrosine. The peptide-surfactant interactions were studied by means of circular dichroism spectroscopy and binding isotherms, as well as by 1D and 2D NMR.

Comparison of the helix-coil transition of a titrating polypeptide in aqueous solutions and at the air-water interface.

The transition from alpha-helix to random coil of the titrating polyamino acid co-poly-L-(lysine, phenylalanine), (p-(Lys,Phe)), has been investigated as a function of pH and ionic strength in aqueous solution and at the air-water interface by means of circular dichroism (CD) spectroscopy and the Langmuir surface film balance technique. The results strongly suggest that the helix-coil transition for peptides at the air-water interface can be determined by using the two-dimensional Flory exponent, nu, to express the pH dependent peptide surface conformation. The helix-coil titration curve of p-(Lys,Phe) shifts approximately 2.

Surveillance for neuraminidase inhibitor resistance in human influenza viruses from Australia.

Two hundred and forty-five human influenza A and B viruses isolated in Australia between 1996 and 2003 were tested for their sensitivity to the NA inhibitor drugs, zanamivir and oseltamivir using a fluorescence-based neuraminidase inhibition assay. Based on mean IC50 values, influenza A viruses (with neuraminidase subtypes N1 and N2) were more sensitive to both the NA inhibitors than were influenza B strains. Influenza A viruses with a N1 subtype and influenza B strains both demonstrated a greater sensitivity to zanamivir than to oseltamivir carboxylate, whereas influenza A strains with a N2 subtype were more susceptible to oseltamivir carboxylate.