J. Appl. Cryst.の発刊に際して

Transition metals occupy an essential niche in biological systems. Their electrostatic properties stabilize substrates or reaction intermediates in the active sites of enzymes, and their heightened reactivity is harnessed for catalysis. However, this heightened activity also renders transition metals toxic at high concentrations. Bacteria, like all living organisms, must regulate their intracellular levels of these elements to satisfy their physiological needs while avoiding harm. It is therefore not surprising that the host capitalizes on both the essentiality and toxicity of transition metals to defend against bacterial invaders. This Review discusses established and emerging paradigms in nutrient metal homeostasis at the pathogen-host interface.

/pdf/nutritional-immunity-transition-metals-at-the-pathogen-host-3wqwttb0ob.pdf

Nutritional immunity: transition metals at the pathogen-host interface.

Simulated gastro-intestinal digestion is widely employed in many fields of food and nutritional sciences, as conducting human trials are often costly, resource intensive, and ethically disputable. As a consequence, in vitro alternatives that determine endpoints such as the bioaccessibility of nutrients and non-nutrients or the digestibility of macronutrients (e.g. lipids, proteins and carbohydrates) are used for screening and building new hypotheses. Various digestion models have been proposed, often impeding the possibility to compare results across research teams. For example, a large variety of enzymes from different sources such as of porcine, rabbit or human origin have been used, differing in their activity and characterization. Differences in pH, mineral type, ionic strength and digestion time, which alter enzyme activity and other phenomena, may also considerably alter results. Other parameters such as the presence of phospholipids, individual enzymes such as gastric lipase and digestive emulsifiers vs. their mixtures (e.g. pancreatin and bile salts), and the ratio of food bolus to digestive fluids, have also been discussed at length. In the present consensus paper, within the COST Infogest network, we propose a general standardised and practical static digestion method based on physiologically relevant conditions that can be applied for various endpoints, which may be amended to accommodate further specific requirements. A frameset of parameters including the oral, gastric and small intestinal digestion are outlined and their relevance discussed in relation to available in vivo data and enzymes. This consensus paper will give a detailed protocol and a line-by-line, guidance, recommendations and justifications but also limitation of the proposed model. This harmonised static, in vitro digestion method for food should aid the production of more comparable data in the future.

https://hal.archives-ouvertes.fr/hal-01209876/document

A standardised static in vitro digestion method suitable for food – an international consensus

Radiometals comprise many useful radioactive isotopes of various metallic elements When properly harnessed, these have valuable emission properties that can be used for diagnostic imaging techniques, such as single photon emission computed tomography (SPECT, eg67Ga, 99mTc, 111In, 177Lu) and positron emission tomography (PET, eg68Ga, 64Cu, 44Sc, 86Y, 89Zr), as well as therapeutic applications (eg47Sc, 114mIn, 177Lu, 90Y, 212/213Bi, 212Pb, 225Ac, 186/188Re) A fundamental critical component of a radiometal-based radiopharmaceutical is the chelator, the ligand system that binds the radiometal ion in a tight stable coordination complex so that it can be properly directed to a desirable molecular target in vivo This article is a guide for selecting the optimal match between chelator and radiometal for use in these systems The article briefly introduces a selection of relevant and high impact radiometals, and their potential utility to the fields of radiochemistry, nuclear medicine, and molecular imaging A description of radiometal-based radiopharmaceuticals is provided, and several key design considerations are discussed The experimental methods by which chelators are assessed for their suitability with a variety of radiometal ions is explained, and a large selection of the most common and most promising chelators are evaluated and discussed for their potential use with a variety of radiometals Comprehensive tables have been assembled to provide a convenient and accessible overview of the field of radiometal chelating agents

Matching chelators to radiometals for radiopharmaceuticals.

https://pubs.rsc.org/en/content/articlepdf/2013/cc/c3cc41143e

Exploration of the medical periodic table: towards new targets

Iron is essential for the proper functioning of all living cells, however it is toxic when present in excess. Thus, using iron chelators as therapeutic agents, namely chelation therapy, has received increasing attention. The objective of this review is to discuss the factors which should be considered when designing clinically useful iron chelators, to present the application of iron chelators in the treatment of iron overload associated with β-thalassaemia major and sickle cell anaemia, and to highlight the potential applications in the treatment of neurodegenerative disorders and microbial infection. This article reviews recent knowledge centred on these themes and indicates the growing importance of the concept of iron chelation in medicine.

Design of iron chelators with therapeutic application

https://www.rsc.org/suppdata/cc/c1/c1cc12123e/c1cc12123e.pdf

Efficient bifunctional gallium-68 chelators for positron emission tomography: tris(hydroxypyridinone) ligands

Carboxymethylated degraded polysaccharides from Enteromorpha prolifera: Preparation and in vitro antioxidant activity.

A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III) A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine This family of dendrimers may find an application in the treatment of iron overload

Iron binding dendrimers: a novel approach for the treatment of haemochromatosis.

The first successful therapeutic iron chelator was desferrioxamine which was introduced in the late 1960's by Ciba (now Novartis). Desferrioxamine has been an extremely successful compound having received the MMW "Pharmaceutical of the year" award for 1991. It is a life saving and a life - prolonging drug which improves the quality of life. However it is not orally active and its administration is both uncomfortable and expensive. Over the past twenty years there has been a growing interest in the orally active iron chelators, deferiprone and exjade, both having been extensively studied. The ability of these compounds to mobilize iron from the heart and endocrine tissue has presented the clinician with some advantages over desferrioxamine. Other orally active iron chelators are currently under development and one, FBS0701 is in clinical trial. The critical features necessary for the design of therapeutically useful iron chelators is presented in this review, together with recent studies devoted to the design of such chelators. This newly emerging range of iron chelators will enable clinicians to apply iron chelation methodology to other disease states and to begin to design personalised chelation regimes.

Tao Zhou

Papers

Design of iron chelators with therapeutic application

Efficient bifunctional gallium-68 chelators for positron emission tomography: tris(hydroxypyridinone) ligands

Carboxymethylated degraded polysaccharides from Enteromorpha prolifera: Preparation and in vitro antioxidant activity.

Iron binding dendrimers: a novel approach for the treatment of haemochromatosis.

Chelating agents for the treatment of systemic iron overload.