Chryssostomos Chatgilialoglu

Italian National Research Council | CNR · Institute for Organic Syntheses and Photoreactivity ISOF

Xeroderma pigmentosum (XP) is characterized by defective repair of ultraviolet-radiation (UVR)-induced DNA damage. Patients have UVR hypersensitivity and increased skin cancer risk. Effective photoprotection has reduced childhood cancer-related deaths, but revealed adolescence-onset neurodegeneration, arising through unknown mechanisms. Here, we in...

Geometrical mono-trans isomers of arachidonic acid (mtAA) are endogenous products of free radical-induced cis-trans double bond isomerization occurring to natural fatty acids during cell metabolism, including lipid peroxidation (LPO). Very little is known about the functional roles of mtAA and in general on the effects of mono-trans isomers of poly...

Plasmalogens are membrane phospholipids with two fatty acid hydrocarbon chains linked to L-glycerol, one containing a characteristic cis-vinyl ether function and the other one being a polyunsaturated fatty acid (PUFA) residue linked through an acyl function. All double bonds in these structures display the cis geometrical configuration due to desat...

Lipid membrane turnover and myelin repair play a central role in diseases and lesions of the central nervous system (CNS). The aim of the present study was to analyze lipid composition changes due to inflammatory conditions. We measured the fatty acid (FA) composition in erythrocytes (RBCs) and spinal cord tissue (gas chromatography) derived from m...

Gestational diabetes mellitus (GDM) is a disorder which manifests itself for the first time during pregnancy and is mainly connected with glucose metabolism. It is also known that fatty acid profile changes in erythrocyte membranes and plasma could be associated with obesity and insulin resistance. These factors can lead to the development of diabe...

Mitochondrial (mt) DNA and nuclear (n) DNA have known structures and roles in cells; however, they are rarely compared under specific conditions such as oxidative or degenerative environments that can create damage to the DNA base moieties. Six purine lesions were ascertained in the mtDNA of wild type (wt) CSA (CS3BE–wtCSA) and wtCSB (CS1AN–wtCSB)...

The consequences of aging and disease conditions in tissues involve reactive oxygen species (ROS) and related molecular alterations of different cellular compartments. We compared a murine model of immunodeficient (SCID) xenografted young (4 weeks old) and old (17 weeks old) mice with corresponding controls without tumor implantation and carried ou...

Hydroxyl radicals (HO•) have long been regarded as a major source of cellular damage. The reaction of HO• with methionine residues (Met) in peptides and proteins is a complex multistep process. Although the reaction mechanism has been intensively studied, some essential parts remain unsolved. In the present study we examined the reaction of HO• gen...

Fatty acids have an important place in both biological and nutritional contexts and, from a clinical point of view, they have known consequences for diseases’ onset and development, including cancer. The use of fatty acid-based food and nutraceuticals to support cancer therapy is a multidisciplinary subject, involving molecular and clinical researc...

Oxygen is important for lipid metabolism, being involved in both enzymatic transformations and oxidative reactivity, and is particularly influent when genetic diseases impair the repair machinery of the cells, such as described for Cockayne syndrome (CS). We used two cellular models of transformed fibroblasts defective for CSA and CSB genes and the...

Trans unsaturated fatty acids in humans may be originated both from dietary supplementation and from an endogenous free-radical-catalyzed cis−trans isomerization of fatty acid residues in naturally occurring cis lipids. The latter process affords geometrical isomers and the polyunsaturated fatty acid mono-trans isomers were demonstrated to be conne...

The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association between signaling cascades and exposure to sapienic acid comparing cell...

Reductive radical stress represents the other side of the redox spectrum, less studied but equally important compared to oxidative stress. The reactivity of hydrogen atoms (H•) and hydrated electrons (e–aq) connected with peptides/proteins is summarized, focusing on the chemical transformations of methionine (Met) and cystine (CysS–SCys) residues i...

Bacteria have evolved several outstanding strategies to resist to compounds or factors that compromise their survival. The first line of defense of the cell against environmental stresses is the membrane with fatty acids as fundamental building blocks of phospholipids. In this review, we focus on a periplasmic heme enzyme that catalyzes the cis-tra...

5’,8-cyclo-2-deoxy nucleosides (cdPus) are the smallest tandem purine lesions including 5’,8-cyclo-2’-deoxyadenosine (cdA) and 5’,8-cyclo-2’-deoxyguanosine (cdG). They can inhibit DNA and RNA polymerases causing mutations, DNA strand breaks, and termination of DNA replication and gene transcription. cdPus can be removed by nucleotide excision repai...

The conversion of ribonucleosides to 2′-deoxyribonucleosides is catalyzed by ribonucleoside reductase enzymes in nature. One of the key steps in this complex radical mechanism is the reduction of the 3′-ketodeoxynucleotide by a pair of cysteine residues, providing the electrons via a disulfide radical anion (RSSR•−) in the active site of the enzyme...

Canine chronic enteropathies (CEs) are inflammatory processes resulting from complex interplay between the mucosal immune system, intestinal microbiome, and dietary components in susceptible dogs. Fatty acids (FAs) play important roles in the regulation of physiologic and metabolic pathways and their role in inflammation seems to be dual, as they e...

The guanyl radical or neutral guanine radical G(-H)• results from the loss of a hydrogen atom (H•) or an electron/proton (e–/H+) couple from the guanine structures (G). The guanyl radical exists in two tautomeric forms. As the modes of formation of the two tautomers, their relationship and reactivity at the nucleoside level are subjects of intense...

Despite the widespread use of silver nanoparticles (AgNPs) in different fields and the amount of investigations available, to date, there are many contradictory results on their potential toxicity. In the present study, extensively characterized 20-nm AgNPs were investigated using optimized protocols and standardized methods to test several toxicol...

Hydroxyl radical (HO•) is the most reactive toward DNA among the reactive oxygen species (ROS) generated in aerobic organisms by cellular metabolisms. HO• is generated also by exogenous sources such as ionizing radiations. In this review we focus on the purine DNA damage by HO• radicals. In particular, emphasis is given on mechanistic aspects for t...

Targeted drug delivery systems represent a promising strategy to treat localised disease with minimum impact on the surrounding tissue. In particular, polymeric nanocontainers have attracted major interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of materials capab...

The originally published article [...]

A new class of DNA intercalating metallodrug is reported. These agents contain a polypyridyl caging ligand called DPA which is bound to a copper ion ligated to a phenanthrene (Phen) DNA intercalator. The lead agent is Cu‐DPA‐DPPZ and it can recognize the minor groove of G–C rich DNA sequences and displays promising activity against several pancreat...

Bleomycin has a long-studied mechanism of action through the formation of a complex with metals, such as iron. Bleomy-cin-iron complex was recently shown to induce membrane damage by free radical reactivity. Since the use of Fe nanoparticles is spreading as drug delivery strategies, molecular mechanisms of cell damage must include different compart...

Molecular-based approaches are rapidly developing in medicine for the evaluation of physiological and pathological conditions and discovery of new biomarkers in prevention and therapy. Fatty acid diversity and roles in health and disease in humans are topical subjects of lipidomics. In particular, membrane fatty acid-based lipidomics provides molec...

Free-radical-mediated processes, such as peroxidation, isomerization and hydrogenation affecting fatty acid integrity and biological functions, have a trans-disciplinary relevance. Cardiolipins (CL, (1,3-diphosphatidyl-sn-glycerol)) and tetra-linoleoyl-CL are complex phospholipids, exclusively present in the Inner Mitochondrial Membrane (IMM) lipid...

Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesion...

We report a series of copper(II) artificial metallo‐nucleases (AMNs) and demonstrate their DNA damaging properties and in vitro cytotoxicity against human‐derived pancreatic cancer cells. The compounds combine a tris‐chelating polypyridyl ligand, di ‐(2‐pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu‐DPA‐...

Free radicals are generated in the biological environment as a result of normal intracellular metabolism. Reactive oxygen species (ROS) function as physiological signalling molecules that participate in the modulation of apoptosis, stress responses and proliferation. ROS can also have a negative effect by causing damages to biomolecules. Therefore,...

Chronic inflammation is estimated to be a causative factor in a variety of diseases. Under inflammatory conditions reactive oxygen species (ROS) and nitrogen species (RNS) are released leading to DNA damage accumulation and genomic instability. Purine 5',8-cyclo-2'-deoxynucleosides (cPu) are oxidative DNA lesions, exclusively derived from the attac...

A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid, a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid has attracted attention as a novel marker of cancer cell plasticity. Here, we analyzed fatty acids, including the n-...

The reaction of HO• radical with DNA is intensively studied both mechanistically and analytically for lesions for-mation. Several aspects related to the reaction paths of purine moieties with the formation of 5’,8-cyclopurines (cPu), 8-oxopurines (8-oxo-Pu) and their relationship are not well understood. In this study, we investigated the reaction...

A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid - a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid attracts attention as novel marker of cancer cell plasticity. Here, we analyzed fatty acids including the n-10 fatt...

Drug delivery systems represent a promising strategy to treat cancer and to overcome the side effects of chemotherapy. In particular, polymeric nanocontainers have attracted major interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of materials capable of responding...

The reaction of hydroxyl radical (HO•) with DNA produces many primary reactive species and many lesions as final products. In this study, we have examined the optical spectra of intermediate species derived from the reaction of HO• with a variety of single- and double-stranded oligodeoxynucleotides and ct-DNA in the range of 1 μs to 1 ms by pulse r...

The natural peptide somatostatin has hormonal and cytostatic effects exerted by the binding to specific receptors in various tissues. Therapeutic uses are strongly prevented by its very short biological half-life of 1–2 min due to enzymatic hydrolysis, therefore encapsulation methodologies are explored to overcome the need for continuous infusion r...

Chronic low-grade inflammation and oxidative stress associated with obesity induce molecular changes in extracellular matrix connected to relaxin pathway and fibrosis, the lipidome of various tissues and the level of lipid mediators. Increase of desaturase enzymatic activity and activation of the inflammatory mediator cascades are known to be assoc...

Purine 5’,8-cyclo-2’-deoxynucleosides (cPu) are tandem-type lesions observed among the DNA purine modifications and identified in mammalian cellular DNA in vivo. These lesions can be present in two diasteroisomeric forms, 5’R and 5’S, for each 2’-deoxyadenosine and 2’-deoxyguanosine moiety. They are generated exclusively by hydroxyl radical attack...

Increased rates of reactive oxygen/nitrogen species (ROS/RNS) are involved in almost all cancer types, associated with tumor development and progression, causing damage to biomolecules such as proteins, nucleic acids and membrane lipids, in different biological compartments. We used a human tumor xenograft mouse model to evaluate for the first time...

Xeroderma pigmentosum (XP) is a genetic disorder associated with defects in nucleotide excision repair, a pathway that eliminates a wide variety of helix-distorting DNA lesions, including ultraviolet-induced pyrimidine dimers. In addition to skin diseases in sun-exposed areas, approximately 25% of XP patients develop progressive neurological diseas...

Palmitic acid metabolism involves delta-9 and delta-6 desaturase enzymes forming palmitoleic acid (9cis-16:1; n-7 series) and sapienic acid (6cis-16:1; n-10 series), respectively. The corresponding biological consequences and lipidomic research on these positional monounsaturated fatty acid (MUFA) isomers are under development. Furthermore, sapieni...

Palmitic acid metabolism involves delta-9 and delta-6 desaturase enzymes forming palmitoleic acid (9cis-16:1; n-7 series) and sapienic acid (6cis-16:1; n-10 series), respectively. The corresponding biological consequences and lipidomic research on these positional MUFA isomers are under development. Furthermore, sapienic acid can bring to the de no...

5’,8-Cyclo-2’-deoxyadenosine (cdA), in the 5’R and 5’Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by the nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the...

The graphic shows a DNA double helix rendered in PyMOL with some of the nucleotides substituted with the copper complexes (in surface dotted form) reported here. The complexes contain planar phenanthrene ligands and these are facing into the double helix as artificial base pairs. The tiles on the left refer to one of our complexes (Cu=copper, PHEN=...

5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the gen...

The non-bulky 5′,8-cyclopurine DNA lesions (cP) and the bulky, benzo[a]pyrene diol epoxide-derived stereoisomeric cis and trans-N2-guanine adducts (BPDE-dG) are good substrates of the human nucleotide excision repair (NER) mechanism. These DNA lesions were embedded at the In or Out rotational settings near the dyad axis in nucleosome core particles...

The use of copper complexes for redox and oxidative-based mechanisms in therapeutic strategies is an important field of multidisciplinary research. Here, a novel Cu(II) complex [Cu(TPMA)(Phen)](ClO4)2 (Cu-TPMA-Phen, where TPMA = tris-(2-pyridylmethyl)amine and Phen = 1,10-phenanthroline) was studied using both the free and encapsulated forms. A hol...

Nanoscale drug delivery systems represent a promising strategy to treat cancer and to overcome the side effects of chemotherapy. In particular, hollow polymeric nanocontainers have attracted great interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of stimuli-respons...

Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is first recognized during pregnancy. It is currently a growing health problem worldwide affecting from 1% to 14% of all pregnant women depending on racial and ethnic group as well as the diagnostic and screening criteria. Our preliminary study aimed at investigating the er...

The building of robust and versatile inorganic scaffolds with artificial metallo‐nuclease (AMN) activity is an important research goal for bioinorganic, biotechnology, and metallodrug research fields. Here we report a new type of AMN combining a tris‐(2‐pyridylmethyl)amine (TPMA) scaffold with the copper(II) N,N′‐phenanthrene chemical nuclease core...

Non-ideal kinetic chain analysis was used to examine the kinetic limitations of free radical synthesis. Homolytic aromatic substitution (HAS: ArH + R• → ArR + H•) occurs in a chain-terminating side-reaction to the tributyltin hydride (SnH) reduction chain (RX + SnH + (i•)cat. → RH + SnX). Kinetic modeling of pre-mixed and slow reagent-addition reac...

Hydrogen sulfide (H2S) was evaluated for its peculiar sulfur radical species generated at different pHs and was used under photolytical conditions in aqueous medium for the reduction of 1,2-diols to alcohols. The conversion steps of 1,2-cyclopentanediol to cyclopentanol via cyclopentanone were analyzed, and it was proven that the reaction proceeds...

This review is an update on tris(trimethylsilyl)silane, TTMSS, in organic chemistry, focusing on the advancements of the past decade. The overview includes a wide range of chemical processes and synthetic strategies under different experimental conditions, including functional group insertion and transformations, as well as preparation of complex m...

Reversible addition of thiyl radicals to cis fatty acids converts them into trans fatty acids, LZ + S• ⇄ SL• ⇄ LE + S•, in a cycle that, uninterrupted, would rapidly isomerize lipids exposed to radicals and thiols. One reason this does not happen in foods and organisms is because the cycle is interrupted – by exothermic allylic abstraction, L + S•...

Unsaturated fatty acids are found in humans predominantly in the cis configuration. Fatty acids in the trans configuration are primarily the result of human processing (trans fats), but can also be formed endogenously by radical stress. The cis–trans isomerization of fatty acids by free radicals could be connected to several pathologies. Trans fats...

Background The widespread use of wireless devices during the last decades is raising concerns about adverse health effects of the radiofrequency electromagnetic radiation (RF‐EMR) emitted from these devices. Recent research is focusing on unraveling the underlying mechanisms of RF‐EMR and potential cellular targets. The “omics” high‐throughput appr...

Unsaturated fatty acids are found in humans predominantly in the cis configuration. Fatty acids in the trans configuration are primarily the result of human processing ( trans fats), but can also be formed endogenously by radical stress. The cis-trans isomerization of fatty acids by free radicals could be connected to several pathologies. Trans fat...

Docosahexaenoic acid (DHA) is a semi-essential polyunsaturated fatty acid (PUFA) for eukaryotic cells, found in natural sources such as fish and algal oils and widely used as ingredient for omega-3 containing foods or supplements. DHA effects are connected to its natural structure with six cis double bonds, but geometrical monotrans isomers can be...