Binding Studies Of Gold Compounds To Human Serum Albumin Utilisng Nmr

Although preliminary data on some novel gold compounds indicate good antiviral activity, further information is required for them to be considered promising lead candidates. As part of our interest in the elucidation of the mode of action of gold based compounds, this work aims to investigate the binding properties of novel gold complexes to human serum albumin (HSA) using saturation transfer difference (STD) NMR technique.

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. Serves as an essential working handbook aimed at scientists and students in medicinal chemistry Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies Discusses improvements in pharmacokinetics from a practical chemist's standpoint

In recent years, the fabrication of nanomaterials and exploration of their properties have attracted the attention of various scientific disciplines such as biology, physics, chemistry, and engineering. Although nanoparticulate systems are of significant interest in various scientific and technological areas, there is little known about the safety of these nanoscale objects. It has now been established that the surfaces of nanoparticles are immediately covered by biomolecules (e.g. proteins, ions, and enzymes) upon their entrance into a biological medium. This interaction with the biological medium modulates the surface of the nanoparticles, conferring a “biological identity” to their surfaces (referred to as a “corona”), which determines the subsequent cellular/tissue responses. The new interface between the nanoparticles and the biological medium/proteins, called “bio-nano interface,” has been very rarely studied in detail to date, though the interest in this topic is rapidly growing. In this book, the importance of the physiochemical characteristics of nanoparticles for the properties of the protein corona is discussed in detail, followed by comprehensive descriptions of the methods for assessing the protein-nanoparticle interactions. The advantages and limitations of available corona evaluation methods (e.g. spectroscopy methods, mass spectrometry, nuclear magnetic resonance, electron microscopy, X-ray crystallography, and differential centrifugal sedimentation) are examined in detail, followed by a discussion of the possibilities for enhancing the current methods and a call for new techniques. Moreover, the advantages and disadvantages of protein-nanoparticle interaction phenomena are explored and discussed, with a focus on the biological impacts.

Research in the pharmaceutical sciences and medicinal chemistry has taken an important new direction in the past two decades with a focus on large molecules, especially peptides and proteins, as well as DNA therapeutics. In Drug Design and Discovery: Methods and Protocols, leading experts provide an in-depth view of key protocols that are commonly used in drug discovery laboratories. Covering both classic and cutting-edge techniques, this volume explores computational docking, quantitative structure-activity relationship (QSAR), peptide synthesis, labeling of peptides and proteins with fluorescent labels, DNA-microarray, zebrafish model for drug screening, and other analytical screening and biological assays that are routinely used during the drug discovery process. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and accessible, Drug Design and Discovery: Methods and Protocols serve as a vital laboratory reference for pharmaceutical chemists, medicinal chemists, and pharmacologists as well as for molecular biologists.

This book contains contributions from interdisciplinary scientists to collectively address the issue of targeting carbohydrate recognition for the development of novel therapeutic and diagnostic agents. The book covers (1) biological problems involving carbohydrate recognition, (2) structural factors mediating carbohydrate recognition, (3) design and synthesis of lectin mimics that recognize carbohydrate ligands with high specificity and affinity, and (4) modulation of biological and pathological processes through carbohydrate recognition.

This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.

Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.

This book presents a critical assessment of progress on the use of nuclear magnetic resonance spectroscopy to determine the structure of proteins, including brief reviews of the history of the field along with coverage of current clinical and in vivo applications. The book, in honor of Oleg Jardetsky, one of the pioneers of the field, is edited by two of the most highly respected investigators using NMR, and features contributions by most of the leading workers in the field. It will be valued as a landmark publication that presents the state-of-the-art perspectives regarding one of today's most important technologies.