Barbara Richichi

University of Florence | UNIFI · Dipartimento di Chimica "Ugo Schiff"

The reversibility of the covalent interaction between boronic acids and 1,2- or 1,3-diols has put the spotlight on this reaction for its potential in the development of sensors and for the fishing of bioactive glycoconjugates. In this work, we describe the investigation of this reaction for the reversible functionalization of the surface of CdSe/Zn...

In this work, we have discovered that the Gal‐α‐(1→3)‐Gal‐β‐(1→3)‐GlcNAc trisaccharide, a fragment of the B antigen Type‐1, is a new ligand of two C‐type lectin receptors (CLRs) i. e. DCAR and Mincle which are key players in different types of autoimmune diseases. Accordingly, we report here on a straightforward methodology to access pure Gal‐α‐(1→...

Liquid‐phase exfoliation (LPE) in aqueous solutions provides a simple, scalable, and green approach to produce 2D materials. By combining atomistic simulations with exfoliation experiments, the interaction between a surfactant and a 2D layer at the molecular scale can be better understood. In this work, two different dyes, corresponding to rhodamin...

A hybrid cellulose-based programmable nanoplatform for applications in precision radiation oncology is described. Here, sugar heads work as tumor targeting moieties and steer the precise delivery of the radiosentizer i.e....

The increasing resistance of bacteria to conventional antibiotics represents a severe global emergency for human health. The broad-spectrum antibacterial activity of silver has been known for a long time, and silver at the nanoscale shows enhanced antibacterial activity. This has prompted research into the development of silver-based nanomaterials...

Covalent functionalization of graphene oxide (GO) with boron dipyrromethenes (BODIPYs) was achieved through a facile synthesis, affording two different GO‐BODIPY conjugates where the main difference lies in the nature of the spacer and the type of bonds between the two components. The use of a long but flexible spacer afforded strong electronic GO‐...

Cellulose nanocrystal and gold nanoparticles are assembled, in a unique way, to yield a novel modular glyconanomaterial whose surface is then easily engineered with one or two different headgroups, by exploiting a robust click chemistry route. We demonstrate the potential of this approach by conjugating monosaccharide headgroups to the glyconanomat...

Biomedical applications of molecules that are able to modulate β-adrenergic signaling have become increasingly attractive over the last decade, revealing that β-adrenergic receptors (β-ARs) are key targets for a plethora of therapeutic interventions, including cancer. Despite successes in β-AR drug discovery, identification of β-AR ligands that are...

Pairing glycans with tissue lectins controls multiple effector pathways in (patho)physiology. A clinically relevant example is the prodegradative activity of galectins-1 and -3 (Gal-1 and -3) in the progression of osteoarthritis (OA) via matrix metalloproteinases (MMPs), especially MMP-13. The design of heterobifunctional inhibitors that can block...

The synthesis and reactivity in an [4+2] inverse electron demand hetero Diels‐Alder reaction (ihDA) of an original class of electron‐poor heterodienes, the N‐substituted‐1H‐benzo[c][1,2]thiazin‐4‐one‐2,2‐dioxides, are described. These are highly reactive electrophiles that allow easy access to unprecedented benzo‐thiazine glyco‐fused derivatives in...

The engineering of the surface of nanomaterials with bioactive molecules allows controlling their biological identity thus accessing functional materials with tuned physicochemical and biological profiles suited for specific applications. Then, the manufacturing process, by which the nanomaterial surface is grafted, has a significant impact on thei...

Carbohydrates are ubiquitous molecules expressed on the surface of nearly all living cells, and their interaction with carbohydrate-binding proteins is critical to many immunobiological processes. Carbohydrates are utilized as antigens in many licensed vaccines against bacterial pathogens. More recently, they have also been considered as adjuvants....

Boron dipyrromethene derivates (BODIPYs) are promising photosensitisers (PSs) for cancer treatment using photodynamic therapy (PDT). This study investigates the functionalisation of graphene oxide (GO) with a BODIPY derivate for glutathione (GSH) depletion and PDT. The functionalisation of GO with a 3,5-dichloro-8-(4-boronophenyl) BODIPY via a diol...

The bioimaging of cancer cells by the specific targeting of overexpressed biomarkers is an approach that holds great promise in the identification of selective diagnostic tools. Tumor-associated human carbonic anhydrase (hCA) isoforms IX and XII have been considered so far as well-defined biomarkers, with their expression correlating with cancer pr...

The success of the rational bottom-up approach to nanostructured carbon materials and the discovery of the importance of their doping with heteroatoms puts under the spotlight all synthetic organic approaches to polycyclic aromatic hydrocarbons. The construction of atomically precise heteroatom doped nanographenes has evidenced the importance of co...

The increased phenomenon of antimicrobial resistance and the slow pace of development of new antibiotics are at the base of a global health concern regarding microbial infections. Antibiotic resistance kills an estimated 700,000 people each year worldwide, and this number is expected to increase dramatically if efforts are not made to develop new d...

A Correction to this paper has been published: https://doi.org/10.1007/s10719-021-09995-7

The custom functionalization of a graphene surface allows access to engineered nanomaterials with improved colloidal stability and tailored specific properties, which are available to be employed in a wide range of applications ranging from materials to life science. The high surface area and their intrinsic physical and biological properties make...

Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen‐specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency vir...

Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell–cell communications and in the regulation of immune responses. Through the interaction with glycan‐binding receptors, glycans are able to affect the ac...

Lectins are involved in a wide range of carbohydrate mediated recognition processes. Therefore, the availability of highly performant fluorescent tools tailored for lectin targeting and able to efficiently track events related to such key targets is in high demand. We report here on the synthesis of the glyco-BODIPYs 1 and 2, based on the efficient...

A conformationally constrained mimetic of l -fucose has been employed to explore whether glycan mimicry could be utilized to interfere with the catalytic activity of α-1,3-fucosyltransferases.

Vaccination has had a formidable positive effect on the quality of public health, essentially eliminating most of the life-threatening infectious diseases and saving millions of lives, in particular infants and young children. In this regard, glycoconjugate vaccines, based on the covalent linking to immunogenic proteins of glycan structures uniquel...

Provided are compositions and methods for specific fucosyltransferase inhibition for the treatment of a variety of diseases. The compositions of the invention comprise a glycomimetic of L-Fucose that selectively inhibits the generation of sialyl Lewis X by FTVI and FTVII but has no effect on the generation of Lewis X by FTIX.

Mechanochemistry is an emerging and reliable alternative to conventional solution (batch) synthesis of complex molecules under green and solvent-free conditions. In this regard, we report here on the conjugation of a dextran polysaccharide with a fluorescent probe, a phenylboronic acid (PBA)-functionalized boron dipyrromethene (BODIPY) applying the...

Mechanochemistry is an emerging and reliable alternative to conventional solution (batch) synthesis of complex molecules under green and solvent-free conditions. In this regard, we report here on the conjugation of a dextran polysaccharide with a fluorescent probe, a phenylboronic acid (PBA)-functionalized boron dipyrromethene (BODIPY) applying the...

Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator associated to diverse homeostatic and signaling roles. Enhanced biosynthesis of S1P, mediated by the sphingosine kinase isozymes (SK1 and SK2), is implicated in several pathophysiological conditions and diseases, including skeletal muscle fibrosis, inflammation, multiple sclerosis and canc...

This article focuses on the synthesis and applications in bioimaging, sensing and therapy of semiconductor Quantum Dots (QDs) coated with carbohydrates (glyco-QDs). After a brief historical excursus on the discovery of semiconductor QDs, the reader will be introduced to the general characteristics of these types of nanomaterials, especially focusin...

We report here on the efficient and straightforward synthesis of a series of modular and functional PBA-BODIPY dyes 1-4. They are an outstanding example of the efficient merge of the versatility of the 3,5-dichloro-BODIPY derivatives and the receptor-like ability of the PBA moiety. The potential bioanalytical applicability of these tools was assess...

We describe a simple method to prepare water dispersible core-shell CdSe/ZnS quantum dots (QDs) 1 capping QDs with the new thiol-containing heterobifunctional dicarboxylic ligand 4 (DHLA-EDADA). This ligand, obtained in gram scale through few synthetic steps, provides a compact layer on the QDs, whose hydrodynamic size in H2O is 15 nm ± 3 nm. The c...

The practical synthesis of novel multivalent fluorescent quantum-dot-based probes to target cellular matrix metalloproteinases (MMPs) (MT-MMPs) is reported. We show that these probes, which are decorated with a nanomolar water-soluble MMP inhibitor, can be used to label preferentially the surface of cancer cells that are known to express MMPs while...

GM3-ganglioside is known to be involved in melanoma proliferation. In order to modulate metastatic-related events, we have functionalized multi-walled carbon nanotubes (MWCNTs) with multiple copies of a GM3-lactone mimetic. The MWCNTs proved to guarantee the proper spatial arrangement of the mimetic allowing a stronger inhibition of migration and i...

Bacterial and fungal pathogens involved in lung infection in cystic fibrosis patients utilize a particular family of glycan-binding proteins, characterized by the presentation of six fucose-binding sites on a ring shape scaffold. These lectins are attractive targets for anti-infectious compounds that could interfere in the recognition of host tissu...

Oxaliplatin (OXA) is a valuable and largely used cancer drug, which induces a serious and intractable neuropathy. The lipoyl-homotaurine derivative, ADM_12, reverts in vivo OXA-induced neuropathy and it is an effective antagonist of the nociceptive sensor channel TRPA1. Unprecedentedly, this safe analgesic showed a synergy with OXA in vitro and pro...

Previous studies proved the effectiveness of an intravenous PEGylated liposomal formulation of opiorphin (1 mg/mL) in protecting the drug from enzymatic degradation, and improving intensity and duration of its painkilling effect. Therefore, considering the advantages of nasal administration, the aim of this work was the development of a liposomal m...

The ability of a rigid α-Tn mimetic (compound 1) to activate murine invariant natural killer T (iNKT) and human natural killer (NK) cells, two subsets of lymphocytes involved in cancer immunesurveillance, was investigated. For this purpose, the mimetic 1 was properly conjugated to a stearic acid containing glycerol-based phospholipid (compound 5) t...

The ability of dendritic cells to coordinate innate and adaptive immune responses makes them essential targets for vaccination strategies. Presentation of specific antigens by dendritic cells is required for the activation of the immune system against many pathogens, and nanoscale materials can be functionalized for active targeting of dendritic ce...

Dendrimers are efficient drug delivery systems particularly useful in ocular diseases. In particular, low generation PAMAM dendrimers are non-toxic and non-immunogenic and they provide an enhancement of the residence time of drugs in the eyes. In this context, the synthesis of the PAMAM-based matrix metalloproteinases inhibitor 5, is reported. In p...

The use of paramagnetic probes is gaining importance in structural biology and drug discovery. Herein, we report the design and synthesis of the Ln3+-complexes of a DOTA-containing inhibitor of matrix metalloproteinases. The tight binding of the sulfonamide scaffold to the catalytic domain of the investigated matrix metalloproteinase was not impair...

Glycosphingolipids (GSLs) are involved in HIV-1 entry. GM-3 ganglioside, a widespread GSL, affects HIV entry and infection in different ways, depending on the concentration, through its anchoring activity in lipid rafts. This explains why the induction of an altered GSLs metabolism appeared a tempting approach to reduce HIV-1 cells infection. This...

Matrix metalloproteinases (MMPs) are peptidases involved in several physiological as well as pathological1. The synthesis of sulfonamide derivatives as matrix metalloproteinsaes inhibitors (MMPIs) was widely investigated, but the lack of selectivity for the targeted tissues and the insolubility in water have dramatically reduced the therapeutic int...

Synthetic sulfonamide derivatives are a class of potent matrix metalloproteinase inhibitors (MMPI) that have potential for the treatment of diseases related to uncontrolled expression of these enzymes. The lack of selectivity of the large majority of such inhibitors, leading to the inhibition of MMPs in tissues other than the targeted one, has dram...

Antibiotic resistance in the opportunistic pathogen Pseudomonas aeruginosa is partly caused by biofilms forming a physical barrier to antibiotic penetration. Here we focused on modifying tetravalent glycopeptide dendrimer ligands of P. aeruginosa lectins LecB or LecA to increase their biofilm inhibition activity. First heteroglycoclusters were inve...

Two tetravalent architectures, the glycocalix 7 and the RAFT 9, presenting four residues of a GM-3 ganglioside lactone mimetic, target the host compartment of melanoma and significantly abrogate the effect induced by cancer-associated fibroblasts (CAFs) contact + hypoxia in the motility and invasiveness of tumor cells. The data reported support the...

A small library of glycofused tricyclic compounds with a central pyran ring chemically modified in the position para to the ring oxygen has been synthesised. The influence of the chemical modification on the structural conformation of the compounds and on their ability to bind Aβ peptide has been evaluated respectively using molecular mechanics (MM...

Cycloadduct 1 is a conformationally constrained mimetic of the tumor-associated Tn antigen. It maintains the 4C1 conformation and the α-O-glycosidic linkage of the natural epitopes. Due to its tricyclic structure, the anomeric linkage is constrained and its conformation “frozen”. Using saturation transfer difference NMR spectroscopy experiments, ep...

Cancer associated fibroblasts (CAFs) are key determinants of cancer progression. In prostate carcinoma (PCa), CAFs induce epithelial-mesenchymal transition (EMT) and metabolic reprogramming of PCa cells towards oxidative phosphorylation (OXPHOS), promoting tumor growth and metastatic dissemination. We herein establish a novel role for pyruvate kina...

In recent years there has been increasing evidence of the importance of carbohydrates and glycoconjugates in biomedical applications, and the use of synthetic ligands based on carbohydrates as drugs has received much attention. Focussing on drug discovery from key targets and placing an emphasis on the multi-disciplinary approaches necessary to cha...

Background Conventional and PEGylated liposomes were developed, aimed at improving the pain-killing effect of opiorphin. Methods The antinociceptive action of the formulations was investigated on rats (tail-flick test), and compared with that of opiorphin and morphine aqueous solutions (all at 5 mg/kg). Results Opiorphin loading in conventional l...

Inflammation of the trigeminal nerve is considered one of the most painful conditions known to humankind. The diagnosis is often difficult; moreover, safe and effective pharmacological treatments are lacking. A new molecule, ADM_12, formed by a lipoic and omotaurine residues covalently linked, is here reported. In vitro and in vivo tests showed tha...

Tumor-associated carbohydrate antigens (TACAs) are key components of cancer vaccines. A variety of vaccines based on native TACAs such as α-Tn have shown immunogenicity and protection in preclinical animal studies, however, their weak immunogenicity, low in vivo instability, and poor bioavailability, have discouraged their further evaluations in cl...

Vaccination strategies based on dendritic cells (DCs) armed with specific tumor antigens have been widely exploited due the properties of these immune cells in coordinating an innate and adaptive response. Here, we describe the convergent synthesis of the bifunctional multivalent glycodendron 5, which contains nine residues of mannose for DC target...

Among new therapies to fight tumors, immunotherapy is still one of the most promising and intriguing. Thanks to the ongoing structural elucidation of several tumor antigens and the development of innovative antigen carriers, immunotherapy is in constant evolution and it is largely used either alone or in synergy with chemotherapy/radiotherapy. With...

Dedicated to Professor Pierre Vogel on the occasion of his 70 th anniversary Abstract The stereoselective synthesis of KDO-based glyco-1,4-oxathiins is described. Relying on a totally diastereoselective inverse electron demand hetero Diels-Alder, α,α′-dioxothiones as electron-poor heterodienes, and glycals as electron-rich dienophiles, reacted to g...

Sialic acids are involved in a plethora of important biological events; among these the most known certainly is the binding of N-acetylneuraminic acid (Neu5Ac) with influenza virus sialidase. Considering Neu5Ac as the template that led to the structure-based development of the two potent antiviral agents zanamivir and oseltamivir, we developed the...

Neuropathic pain (NeP) is generally considered an intractable problem, which becomes compelling in clinical practice when caused by highly effective chemotherapeutics, such as in the treatment of cancer with oxaliplatin (OXA) and related drugs. In the present work we describe a structurally new compound, ADM_09, which proved to effectively revert O...

A TRPA1 antagonist reverts oxaliplatin-induced neuropathic pain

Burkholderia ambifaria is a bacterium member of the Burkholderia cepacia complex (BCC), a closely related group of Gram-negative bacteria responsible for "cepacia syndrome" in immunocompromised patients. B. ambifaria produces BambL, a fucose-binding lectin that displays fine specificity to human fucosylated epitopes. Here, we report the first examp...

Extracellular acidification, a mandatory feature of several malignancies, has been mainly correlated with metabolic reprogramming of tumor cells toward Warburg metabolism, as well as to the expression of carbonic anydrases or proton pumps by malignant tumor cells. We report herein that for aggressive prostate carcinoma, acknowledged to be reprogram...

A new strategy to exploit galectin presence to target matrix metalloproteinases (MMPs) is presented. A bifunctional conjugate with lactose and an inhibitor for MMPs is able to bind MMP and Gal-3 simultaneously. This compound might allow the lectin to attract MMPI to the tumour site and to block protumoural activities of the lectin at the same time.

Key Points The mechanism of bone marrow failure (BMF) in PNH is not known. Novel CD1d-restricted, GPI-specific T cells are present in PNH patients and might be responsible for BMF.

Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response....

647 PNH is caused by somatic mutations in the PIG-A gene in hematopoietic stem cells leading to disruption of the synthesis of GPI, a glycolipid used for post-translational modification of proteins. PNH is classically characterized by the triad of intravascular hemolysis, severe acquired thrombophilia and multiple cytopenias. Whereas the first two...

The interactions between carbohydrates and proteins have been extensively explored in a wide range of physiological and pathological processes over several decades. The recent emergence of glycomics has strengthened this interest and notably contributed to spectacular progress in understanding how carbohydrates mediate and regulate complex biologic...

The biological role of GPI anchors is of paramount importance; however, we are still far from fully understanding the structure-function relationship of these molecules. One major limiting factor has been the tiny quantities available from natural sources; obtaining homogeneous and well-defined GPI structures by synthesis, is both a challenge and a...

N-arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the...