A5027617278- Chemical Synthesis and Analysis
- HIV/AIDS drug development and treatment
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- HIV Research and Treatment
- Protein Structure and Dynamics
- Surfactants and Colloidal Systems
- Analytical Chemistry and Chromatography
- Biochemical and Molecular Research
- Drug Transport and Resistance Mechanisms
- Drug Solubulity and Delivery Systems
- Neuropeptides and Animal Physiology
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Crystallization and Solubility Studies
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Pharmacogenetics and Drug Metabolism
- Click Chemistry and Applications
- Supramolecular Self-Assembly in Materials
- Antimicrobial Peptides and Activities
- Enzyme Structure and Function
- Synthesis and biological activity
- Mass Spectrometry Techniques and Applications
- X-ray Diffraction in Crystallography
Monash University
2016-2025
Quotient Clinical (United Kingdom)
2017-2024
Australian Regenerative Medicine Institute
2017-2022
Institute of Medicinal Plant Development
2000-2015
Crystal Research (United States)
2012
Novita Healthcare (Australia)
2011
St Vincents Institute of Medical Research
2010
NAACP Legal Defense and Educational Fund
2009
Utah State University
2003
Washington University in St. Louis
1995-1996
Underpinning all drug discovery projects is the interaction between a and its target, usually protein. Thus, improved methods for predicting magnitude of protein–ligand interactions have potential to improve efficiency development. In this review, we describe principles free energy used calculation binding energies, challenges associated with these methods, recent advances developed address difficulties. We then present case studies from 2005 2017, each demonstrating that alchemical can...
A structure-activity relationship (SAR) guided design of novel tubulin polymerization inhibitors has resulted in a series benzo[b]furans with exceptional potency toward cancer cells and activated endothelial cells. The early lead compounds been substantially improved through the synergistic effect introducing conformational bias additional hydrogen bond donor to pharmacophore. Screening focused library potent for selectivity against over quiescent afforded...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPro-D-NMe-Amino Acid and D-Pro-NMe-Amino Acid: Simple, Efficient Reverse-Turn ConstraintsDavid K. Chalmers Garland R. MarshallCite this: J. Am. Chem. Soc. 1995, 117, 22, 5927–5937Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/ja00127a004https://doi.org/10.1021/ja00127a004research-articleACS PublicationsRequest reuse permissionsArticle...
The antiviral treatment of chronic hepatitis B is limited by the selection resistance mutations. Primary to lamivudine occurs at rtM2041/V in C Domain polymerase. Recently, adefovir has also been described D rtN236T. patients with resistant virus without complete suppression can lead further compensatory Thus, gain an understanding (HBV) polymerase and mutations associated resistance, a three-dimensional model HBV reverse transcriptase core region based on homology human immunodeficiency...
We report the development of homology models dopamine (D2, D3, and D4), serotonin (5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C), histamine (H1), muscarinic (M1) receptors, based on high-resolution structure β2-adrenergic receptor. The were built refined using Prime. have addressed required modeling extracellular loop 2, which is often implicated in ligand binding. orthosteric sites optimized induced fit docking, to allow for side-chain flexibility, resulting receptor been evaluated protein validation...
Fragment screening is becoming widely accepted as a technique to identify hit compounds for the development of novel lead compounds. In neighboring laboratories, we have recently, and independently, performed fragment campaign on HIV-1 integrase core domain (IN) using similar commercially purchased libraries. The two campaigns used different methods preliminary identification hits; one saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR), other surface plasmon...
The ability of lipid-based formulations (LBFs) to increase the solubilization, and prolong supersaturation, poorly water-soluble drugs (PWSDs) in gastrointestinal (GI) fluids has generated significant interest past decade. One mechanism enhance utility LBFs is supersaturation via addition polymers that inhibit drug precipitation (polymeric inhibitors or PPIs) formulation. In this work, we have evaluated performance a range PPIs identified are sufficiently soluble LBF allow construction...
Abstract α-adrenergic receptors (αARs) are G protein-coupled that regulate vital functions of the cardiovascular and nervous systems. The therapeutic potential αARs, however, is largely unexploited hampered by scarcity subtype-selective ligands. Moreover, several aminergic drugs either show off-target binding to αARs or fail interact with desired subtype. Here, we report crystal structure human α 1B AR bound inverse agonist (+)-cyclazosin, enabled fusion a DARPin crystallization chaperone....
Dimeric derivatives (compounds 7 to 9) of the influenza virus neuraminidase inhibitor zanamivir (compound 2), which have linking groups 14 18 atoms in length, are approximately 100-fold more potent inhibitors replication vitro and vivo than zanamivir. The observed optimum linker length 22 A, together with observations that dimers cause aggregation isolated tetramers whole virus, indicate benefit from multivalent binding via intertetramer intervirion linkages. outstanding long-lasting...
Chemogenomics methods seek to characterize the interaction between drugs and biological systems are an important guide for selection of screening compounds. The acid/base character has a profound influence on their affinity receptor, absorption, distribution, metabolism, excretion toxicity (ADMET) profile way drug can be formulated. In particular, charge state molecule greatly influences its lipophilicity biopharmaceutical characteristics. This study investigates human small-molecule drugs,...
Bile components play a significant role in the absorption of dietary fat, by solubilizing products fat digestion. The poorly water-soluble drugs from gastrointestinal tract is often enhanced interaction with pathways digestion and absorption. These processes can enhance drug Thus, phase behavior bile digested lipids great interest to pharmaceutical scientists who seek optimize solubilization gut lumen. This be achieved dosing after food or preferably formulating lipid-based delivery system....
Novel X-ray crystal structures of cyclic <sc>d</sc>/<sc>l</sc> peptide nanotubes in antiparallel and parallel configurations.
A wide range of drug targets can be effectively modulated by peptides and macrocycles. Unfortunately, the size polarity these compounds prevents them from crossing cell membrane to reach target sites in cytosol. As such, do not conform standard measures drug-likeness exist beyond rule-of-five space. In this work, we investigate whether prodrug moieties that mask hydrogen bond donors applied domain improve permeation macrocyclic compounds. Using a cyclic peptide model, show masking natural...
A pharmacophore-based screen identified 32 compounds including ethyl 5-amino-3-(4-tert-butylphenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate (8) as a new allosteric modulator of the adenosine A1 receptor (A1AR). On basis this lead, various derivatives were prepared and evaluated for activity at human A1AR. number test allosterically stabilized agonist-receptor-G protein ternary complexes in dissociation kinetic assays, but found to be more potent antagonists subsequent...
Lipid-based drug formulations can greatly enhance the bioavailability of poorly water-soluble drugs. Following oral administration containing tri- or diglycerides, digestive processes occurring within gastrointestinal (GI) tract hydrolyze glycerides to mixtures free fatty acids and monoglycerides that are, in turn, solubilized by bile. The behavior drugs resulting colloidal is currently not well characterized. This work presents matched vitro experimental molecular dynamics (MD) theoretical...
Polymer‐conjugated peptides are attractive building blocks for the construction of new nanomaterials. However, ability to control self‐assembly these materials remains a major limitation their wider utilization. Herein, we report facile strategy fine‐tune assembly water‐soluble hydrophilic polymer‐conjugated cyclic by incorporating defined, short hydrocarbon linker between polymer and peptide. This addition creates well‐defined hydrophobic ‘inner shell’ that suppresses water from disrupting...
Polymer‐conjugated peptides are attractive building blocks for the construction of new nanomaterials. However, ability to control self‐assembly these materials remains a major limitation their wider utilization. Herein, we report facile strategy fine‐tune assembly water‐soluble hydrophilic polymer‐conjugated cyclic by incorporating defined, short hydrocarbon linker between polymer and peptide. This addition creates well‐defined hydrophobic ‘inner shell’ that suppresses water from disrupting...
Novel, highly constrained, 6,5-bicyclic dipeptides (1-aza-5-oxa-2-oxobicyclo[4.3.0]nonane ring skeletons, 2) have been synthesized by a one-step electrochemical cyclization from the Boc-(S)-serine-(S)-proline-OMe (Boc-(S)-Ser-(S)-Pro-OMe, 3) and Boc-(R,S)-α-methylserine-(S)-proline-OMe (Boc-(R,S)-α-MeS-(S)-Pro-OMe, 12) in yields of 10−25% 41%, respectively. The one-pot reaction uses selective anodic amide oxidation to generate an N-acyliminium cation which is trapped intramolecular hydroxyl...
1 The methodology and interim results of a post marketing surveillance captopril, the first orally active angiotensin converting enzyme inhibitor are presented. 2 Utilising viewdata technology, details hypertensive patients were entered directly into mainframe computer. This allowed day to monitoring events; facility not available with paper‐based methods. 3 design study analysis including some efficacy, concomitant therapy, any disease symptoms reasons for withdrawal. These factors could be...