Stefano d'errico

• PhD
• University of Naples Federico II

The natural compound orotic acid and its anionic form, orotate, play a pivotal role in various biological processes, serving as essential intermediates in pyrimidine de novo synthesis, with demonstrated connections to dietary, supplement, and neurodrug applications. A novel perspective on biomolecular aggregation at the nanoscale, particularly pert...

Porous silicon is one of the most explored nanostructured materials in various biomedical applications owing to its remarkable properties. However, its inherent chemical instability mandates a robust surface modification procedure, and proper surface bioengineering is essential to ensure its effectiveness in the biomedical field. In this study, we...

Herein, we report the structure-based selection via molecular docking of four N-heterocyclic bis-carbene gold(I) complexes, whose potential as ligands for the hTel23 G-quadruplex structure has been investigated using circular dichroism (CD) spectroscopy, CD melting, and polyacrylamide gel electrophoresis (PAGE). The complex containing a bis(1,2,3,4...

Peptide Nucleic Acids (PNAs) represent a promising tool for gene modulation in anticancer treatment. The uncharged peptidyl backbone and the resistance to chemical and enzymatic degradation make PNAs highly advantageous to form stable hybrid complexes with complementary DNA and RNA strands, providing higher stability than the corresponding natural...

This Special Issue, “Molecules from Side Reactions II”, belongs to the section Organic Synthesis of the journal Molbank and was launched in 2021, after the first edition, “Molecules from Side Reactions” [...]

G-wires are supramolecular DNA structures based on the G-quadruplex (G4) structural motif obtained by the self- assembly of interlocked slipped G-rich oligonucleotide (ON) strands, or by end-to-end stacking of G4 units. Despite the increasing interest towards G-wires due to their potential applications in DNA nanotechnologies, the self-assembly pro...

After the fortuitous discovery of the anticancer properties of cisplatin, many Pt(II) complexes have been synthesized, to obtain less toxic leads which could overcome the resistance phenomena. Given the importance of nucleosides and nucleotides as antimetabolites, studying their coordinating properties towards Pt(II) ions is challenging for bioorga...

Redox‐responsive silica drug delivery systems are synthesized by aeco‐friendly diatomite source to achieve on‐demand release of peptide nucleic acid (PNA) in tumor reducing microenvironment, aiming to inhibit the immune checkpoint programmed cell death 1 receptor/programmed cell death receptor ligand 1 (PD‐1/PD‐L1) in cancer cells. The nanoparticle...

i-Motifs, also known as i-tetraplexes, are secondary structures of DNA occurring in cytosine-rich oligonucleotides (CROs) that recall increasing interest in the scientific community for their relevance in various biological processes and DNA nanotechnology. This study reports the design of new structurally modified CROs, named Double-Ended-Linker-C...

The purpose of this Special Issue is to collect papers reporting on, but not limited to, oligonucleotide synthesis, biochemical and biophysical characterization of nucleic acids, new oligonucleotidebased delivery systems, as well as biomaterial and polymer development.

Trans-polydatin (tPD), the 3-β-D-glucoside of the well-known nutraceutical trans-resveratrol, is a natural polyphenol with documented anti-cancer, anti-inflammatory, cardioprotective, and immunoregulatory effects. Considering the anticancer activity of tPD, in this work, we aimed to explore the binding properties of this natural compound with the G...

Alzheimer’s disease (AD) is a chronic, complex neurodegenerative disorder mainly characterized by the irreversible loss of memory and cognitive functions. Different hypotheses have been proposed thus far to explain the etiology of this devastating disorder, including those centered on the Amyloid-β (Aβ) peptide aggregation, Tau hyperphosphorylation...

We herein report an innovative antisense approach based on Peptide Nucleic Acids (PNAs) to down-modulate CD5 expression levels in chronic lymphocytic leukemia (CLL). Using bioinformatics tools, we selected a 12-mer tract of the CD5 mRNA as the molecular target and synthesized the complementary and control PNA strands bearing a serine phosphate dipe...

Cyclic adenosine diphosphate ribose (cADPR) is a cyclic nucleotide involved in the Ca2+ homeostasis. In its structure, the northern ribose, bonded to adenosine through an N1 glycosidic bond, is connected to the southern ribose through a pyrophosphate bridge. Due to the chemical instability at the N1 glycosidic bond, new bioactive cADPR derivatives...

Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epi...

Cyclic adenosine diphosphate ribose (cADPR) is a second messenger involved in the Ca²⁺ homeostasis. Its chemical instability prompted researchers to tune point by point its structure, obtaining stable analogues featuring interesting biological properties. One of the most challenging derivatives is the cyclic inosine diphosphate ribose (cIDPR), in w...

Cystic fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs re...

The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration...

Zinc oxide nanowires (ZnONWs) are largely used in biosensing applications due to their large specific surface area, photoluminescence emission and electron mobility. In this work, the surfaces of ZnONWs are modified by covalent bioconjugation of a peptidic nucleic acid (PNA) probe whose sequence is properly chosen to recognize a complementary DNA (...

Organic synthesis is a powerful tool that allows researchers to express their scientific creativity [...]

Cyclic ADP-ribose (cADPR, 1, Figure 1) is a naturally occurring metabolite of NAD+capable of mobilizing Ca2+ ions from intracellular stores. [...]

In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars 10a–b and 11a–b based on the one-pot conjugation of both enantiomeric forms of N-butyldeoxynojirimycin (NBDNJ) and N-nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction...

Cystic Fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs re...

The interest in DNA based nanostructures arises from their potential applications in diagnostics and drug delivery and in the development of new hybrid and conducting materials. Guanine-rich oligonucleotides can multimerize forming long and stable supramolecular structures, known as G-wires, based on the G-quadruplex (G4) motif. Herein, we report a...

Herein, we reported on the synthesis of a novel Pt(II) neutral complex having as ligand the nucleoside tubercidin, a potent anti-tumor agent extracted from the bacterium Streptomyces Tubercidicus. In detail, the chelation of the metal by a diamine linker installed at C6 purine position of tubercidin assured the introduction of a cisplatin-like unit...

ε-poly-l-Lysine (ε-PLL) peptide is a product of the marine bacterium Bacillus subtilis with antibacterial and anticancer activity largely used worldwide as a food preservative. ε-PLL and its synthetic analogue α,ε-poly-l-lysine (α,ε-PLL) are also employed in the biomedical field as enhancers of anticancer drugs and for drug and gene delivery applic...

In this paper, we report on the synthesis and spectroscopic characterization of the novel nucleoside 5′-chloro-5′-deoxy-2′,3′-O-isopropylidene-6-fluoro nebularine, obtained as a side product during the second step of the synthesis of 5′-fluoro-5′-deoxy-5-aminoimidazole-4-carboxamide-β-d-riboside (5′-F-AICAR), a non-phosphorylable analogue of 5-amin...

Dear Colleagues, As the Guest Editor of the Special Issue of the journal Molbank entitled "Molecules from Side Reactions", it is my pleasure to invite you to submit a short note or communication on this topic. You can see more details about this Special Issue by following the link below: https://www.mdpi.com/journal/molbank/special_issues/side_r...

Herein, we report on the synthesis of a small set of linear precursors of an inosine analogue of cyclic ADP-ribose (cADPR), a second messenger involved in Ca2+ mobilization from ryanodine receptor stores firstly isolated from sea urchin eggs extracts. The synthesized compounds were obtained starting from inosine and are characterized by an N1-alkyl...

G-quadruplexes (G4s) are unusual secondary structures of DNA occurring in guanosine-rich oligodeoxynucleotide (ODN) strands that are extensively studied for their relevance to the biological processes in which they are involved. In this study, we report the synthesis of a new kind of G4-forming molecule named double-ended-linker ODN (DEL-ODN), in w...

The development of new strategies for enhancing drug delivery to the brain represents a major challenge in treating cerebral diseases. In this paper, we report on the synthesis and structural characterization of a biocompatible nanoparticle (NP) made up of poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) co-polymer (namely PELGA) func...

Herein, we reported on the synthesis of cpIPP, which is a new structurally-reduced analogue of cyclic ADP-ribose (cADPR), a potent Ca2+-releasing secondary messenger that was firstly isolated from sea urchin eggs extracts. To obtain cpIPP the "northern" ribose of cADPR was replaced by a pentyl chain and the pyrophosphate moiety by a phophono-phosph...

By combining the ability of short G-rich oligodeoxynucleotides (ODNs) containing the sequence 5'CGGA3' to form higher-order G-quadruplex (G4) complexes with the tetra-end-linked (TEL) concept to produce aptamers targeting the HIV envelope glycoprotein 120 (gp120), three new TEL-ODNs (1–3) having the sequence 5'CGGAGG3' were synthesized with the aim...

Herein, we report on the synthesis and the evaluation of preliminary antitumor properties of a small collection of platinum(II) complexes in which a cisplatin-like unit is tethered to 7-deazaadenosine through linear alkyl chains (from 1 to 6 carbon atoms) installed at the C6 purine position. The complexation is performed by exploiting the reactivit...

Cystic Fibrosis (CF) is one of the most common life shortening conditions in Caucasians. CF is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene which result in reduced or altered CFTR functionality. Several microRNAs (miRNAs) downregulate the expression of CFTR, thus causing or exacerbating the symptoms of CF. In this c...

Obtaining DNA nanostructures with potential applications in drug discovery, diagnostics, and electronics in a simple and affordable way represents one of the hottest topics in nanotechnological and medical sciences. Herein, we report a novel strategy to obtain structurally homogeneous DNA G-wire nanostructures of known length, starting from the sho...

Supplementary

A thorough investigation of the minor oxidation products of two penta-tetrahydrofuran compounds with pyridinium chlorochromate has been carried out. Isolation of ring-B oxygenated spiroketal and degradation products, including polycyclic mono- and bis-lactone compounds, supports the previously postulated involvement of cyclic enolether intermediate...

The title compound, C12H20N4O5, crystallizes in the monoclinic space group P21, with four crystallographically independent mol­ecules in the asymmetric unit. The four mol­ecules have a very similar conformation that is basically determined by the formation of two intra­molecular hydrogen bonds between the amino NH2 donors and the carbonyl and ring...

Background: G-quadruplex DNA is involved in many physiological and pathological processes. Both clinical and experimental studies on DNA G-quadruplexes are slowed down by their enzymatic instability. In this frame, more stable chemically modified analogs are needed. Methods: The bis-end-linked-(gggt)2 PNA molecule (BEL-PNA) was synthesized using...

By using a new rapid screening platform set on molecular docking simulations and fluorescence quenching techniques, three new anti-HIV aptamers targeting the viral surface glycoprotein 120 (gp120) were selected, synthesized and assayed. The use of the short synthetic fluorescent peptide V35-Fluo mimicking the V3 loop of gp120, as the molecular targ...

Cyclic N (1)-pentylinosine monophosphate (cpIMP), a novel simplified inosine derivative of cyclic ADP-ribose (cADPR) in which the N (1)-pentyl chain and the monophosphate group replace the northern ribose and the pyrophosphate moieties, respectively, was synthesized. The role played by the position of the phosphate group in the key cyclization step...

This unit contains four basic protocols describing the synthesis of 5-aminoimidazole-4-carboxamide riboside (AICAR), 5-aminoimidazole-4-carboxamide riboside (ZPM), their 4-N functionalized derivatives, and two sugar-modified analogs of AICAR. The first and second basic protocols reveal the importance of solid-phase synthesis to obtain novel AICAR a...

Herein, the synthesis of a nucleoside platinum(II) complex in which a cisplatin-like unit is joined to 7-deazaadenosine through an amino alkyl chain installed at the C6 position of purine was explored. The capability of the new complex to react with DNA purine bases was confirmed by a model reaction with deoxyguanosine monophosphate, whereas its an...

5-Aminoimidazole-4-carboxamide riboside (AICAR) has an important role in the regulation of the cellular metabolism showing a broad spectrum of therapeutic activities against different metabolic processes. Due to these proven AICAR properties, we have designed, synthesized and tested the biological activity of two ribose-modified AICAR derivatives,...

Steroids are a class of hormones improperly used in livestock as growth promoting agents. Due to their high risk on human health, the European Union (EU) has strictly forbidden the administration of all naturally and synthetic steroid hormones to food-producing animals and the development of new rapid methods are greatly encouraged. In this work, w...

The combined use of silanes (Et3SiH or PMHS) and I2 as novel N-glycosidation reagents for the synthesis of bioactive oxathiolane nucleosides 3TC and FTC is reported. Both systems (working as anhydrous HI sources) were devised to act as substrate activators and N-glycosidation promoters. Excellent results in terms of chemical efficiency and stereose...

A general synthesis of C6-pyridylpurine nucleosides is described. The reported synthetic procedure exploits the regioselective addition of pyridinyl Grignard reagents, obtained by bromine/magnesium exchange between mono- or dihalopyridines and iPrMgCl, to the C6–N1–O– moiety of nebularine N1-oxide. The regioselective transmetallation of unsymmetric...

In a previous work we have demonstrated that the DNA sequence CGGTGGT folds into a higher order G-quadruplex structure (2Q), obtained by the 5'-5' stacking of two unusual G(:C):G(:C):G(:C):G(:C) planar octads belonging to two identical tetra-stranded parallel quadruplexes, when annealed in the presence of ammonium or potassium ions. In the present...

The synthesis of four novel platinum complexes, bearing N6-(6-amino-hexyl)adenosine or a 1,6-di(adenosin-N6-yl)-hexane respectively, as ligands of mono-functional cisplatin or monochloro(ethylendiamine)platinum(II), is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of the adenosine base sy...

Rapid screening tests in medical diagnostic and environmental analysis are often based on oligonucleotide biochips. In this paper, we studied the stability of functionalized mesoporous silicon supports in the solid-phase synthesis of oligonucleotides, exploiting several chemical procedures. A 19-mer mixed sequence has been successfully synthesized...

Computational techniques, and in particular molecular dynamics (MD) simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid- (PNA-) RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of...

Computational techniques, and in particular molecular dynamics (MD) simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid-(PNA-) RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of...

Computational techniques, and in particular molecular dynamics (MD) simulations, have been successfully used as a complementary technique to predict and analyse the structural behaviour of nucleic acids, including peptide nucleic acid-(PNA-) RNA hybrids. This study shows that a 7-base long PNA complementary to the seed region of miR-509-3p, one of...

Recently, microRNAs (miRNAs) were identified as being able to inhibit the expression of the Cystic Fibrosis Transmembrane Regulator (CFTR) disease-gene of Cystic Fibrosis (CF) and CFTR-Related Disorders (CFTR-RD). This study shows the use of peptide nucleic acids (PNAs) as inhibitors of miR-509-3p, one of the CFTR regulating miRNAs, by reverting th...

The synthesis of 2,6-dialkyl(aryl)purine nucleosides by application of a double addition of Grignard reagents to N1-oxide purine nucleosides is described. The synthetic protocol exploits the reactivity of both the C6–N1–O– and C2–N1–O– moieties of the purine base. The overall process consists of initial Grignard reagent addition to the C6 of nebula...

The antiviral activity of certain acyclic nucleosides drew our attention to the fact that the replacement of the furanose ring by an alkyl group bearing hydroxyl(s) could be a useful structural modification to modulate the biological properties of those nucleosides. Herein, we report on the synthesis of some novel acadesine analogues, where the rib...

The first general synthesis of bis-α-acyloxy-1,4- and -1,5-diketones has been accomplished in a catalytic oxidative opening of bis-acylated THF and THP (tetrahydropyran) diols, which were synthesised by osmium- or ruthenium-catalysed oxidative cyclisation of 1,5- and 1,6-dienes. The overall sequence corresponds to the regioselective double ketoacyl...

The substitution of a hydroxyl group by a fluorine atom in a potential drug is an efficient reaction that can, in principle, improve its pharmacological properties. Herein, the synthesis of the novel compound 5'-fluoro-5'-deoxyacadesine (5'-F-AICAR), a strict analogue of AICAR that cannot be 5'-phosphorylated to ZMP by cellular kinases, is reported...

An acyclic pyrimidine analogue, containing a five member cycle fused on the pyrimidine ring, was synthesized and introduced at position 7 or 12 of the 15-mer oligodeoxynucleotide GGTTGGTGTGGTTGG, known as Thrombin Binding Aptamer (TBA). Characterization by 1H-NMR and CD spectroscopies of the resulting aptamers, TBA-T7b and TBA-T12b, showed their ab...