Biomedical subjects

Stephanie Allen

Publications and source records attributed to Stephanie Allen.

21 records · Page 2Linked to original sources

PubMed2002

Differential scanning calorimetry and scanning thermal microscopy analysis of pharmaceutical materials.

Micro-thermal analysis (microTA) by scanning thermal microscopy is being used increasingly for the analysis of pharmaceutical dosage forms. However, there is currently little evidence to show that microTA data can compare directly with that from the established approach of differential scanning calorimetry (DSC). This work compares DSC and microTA data from an active vitamin B6 analogue, pyridoxal hydrochloride, and two commonly used pharmaceutical excipients, Mannitol and Avicel which are used in its formulation. It is found that microTA provides precise and accurate micro-thermal analytical data with 0.1 K thermal sensitivity, which is comparable to that obtained by DSC measurements of bulk samples. It is also shown that microTA offers the opportunity to study single particles and the interfacial region between particles, data which is currently inaccessible through the DSC technique.

Calorimetry, Differential Scanning↗

PubMed2002

Discriminating small molecule DNA binding modes by single molecule force spectroscopy.

Drugs may interact with double stranded DNA via a variety of binding modes, each mode giving rise to a specific pharmacological function. Here we demonstrate the ability of single molecule force spectroscopy to discriminate between different interaction modes by measuring the mechanical properties of DNA and their modulation upon the binding of small molecules. Due to the unique topology of double stranded DNA and due to its base pair stacking pattern, DNA undergoes several well-characterised structural transitions upon stretching. We show that small molecule binding markedly affects these transitions in ways characteristic to the binding mode and that these effects can be detected at the level of an individual molecule. The minor groove binder berenil, the crosslinker cisplatin and the intercalator ethidium bromide are compared.

Bacteriophage lambda↗

PubMedDate not supplied

Molecular level investigations of the inter- and intramolecular interactions of pH-responsive artificial triblock proteins.

Intelligent materials that can undergo physical gelation in response to environmental stimuli have potential impacts in the bioengineering and biomedical fields where the entrapment of cellular or molecular species is desired. Here, we utilize atomic force microscopy (AFM) to perform molecular level investigations of designer artificial proteins that undergo physical gelation. These are engineered as triblock copolymers with independent interchain binding and solvent retention functions, namely, two terminal leucine zipper-like peptide sequences and a central alanylglycine rich sequence, respectively. AFM force measurements between probes and surfaces functionalized with molecules of this triblock protein revealed adhesive interactions that increased in average force and frequency as the pH was lowered from pH 11.2 to 7.4 to 4.5, reflecting an increase in the numbers of interacting molecular strands. In bulk solution, lowering the pH results in a viscous liquid to gel transition. The modular design of the triblock protein was also exploited for single molecule force spectroscopy investigations, which revealed altered intramolecular interactions in response to changes in pH. An increased understanding of the inter- and intramolecular forces involved in biomolecule driven gelation processes is not only of great fundamental interest in the study of the biomolecular systems involved but may also prove key in enabling the rational design of new generations of intelligent hydrogel systems.

Amino Acid Sequence↗