Paolo Rovero

Paolo Rovero
University of Florence | UNIFI · Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino

About

355
Publications
17,738
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6,999
Citations
Citations since 2016
55 Research Items
1337 Citations
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2016201720182019202020212022050100150200
2016201720182019202020212022050100150200

Publications

Publications (355)
Article
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We report for the first time Antibody-Drug-Conjugates (ADCs) containing human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) directed Monoclonal Antibodies (MAbs) linked to low molecular weight inhibitors of the same enzymes by means of hydrophilic peptide spacers. In agreement with the incorporated CA directed MAb fragments, in vitro inhibition data of t...
Article
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The peptide hormone relaxin (RLX), also available as clinical-grade recombinant protein (serelaxin), holds great promise as a cardiovascular and anti-fibrotic agent but is limited by the pharmacokinetic issues common to all peptide drugs. In this study, by a computational modelling chemistry approach, we have synthesized and tested a set of low mol...
Article
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The combination of pharmacologic and endoscopic therapies is the gold standard for treating intestinal failures. The possibility of chemical solubility in water is mandatory for intelligent capsules. Functionalised silk fibroin with peptides and covalently linking different molecular entities to its structure make this protein a platform for prepar...
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The involvement of Myelin Basic Protein (MBP) in Multiple Sclerosis (MS) has been widely discussed in the literature. This intrinsically disordered protein has an interesting α-helix motif, which can be considered as a conformational epitope. In this work we investigate the importance of the helical structure in antibody recognition by MBP peptides...
Article
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The currently devastating pandemic of severe acute respiratory syndrome known as coronavirus disease 2019 or COVID-19 is caused by the coronavirus SARS-CoV-2. Both the virus and the disease have been extensively studied worldwide. A trimeric spike (S) protein expressed on the virus outer bilayer leaflet has been identified as a ligand that allows t...
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Two isoforms of the glutamate decarboxylase (GAD) enzyme exist, GAD65 and GAD67, which are associated with type 1 diabetes (T1D) and stiff-person syndrome (SPS), respectively. Interestingly, it has been reported that T1D patients seldom develop SPS, whereas patients with SPS occasionally develop T1D. In addition, coxsackievirus B4 (CVB4) has previo...
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Despite the global interest and the unprecedented number of scientific studies triggered by the COVID-19 pandemic, few data are available from developing and low-income countries. In these regions, communities live under the threat of various transmissible diseases aside from COVID-19, including malaria. This study aims to determine the severe acut...
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A growing industrial interest toward the peptide drug market fueled the need for the development of effective and cGMP compliant manufacturing methods for these complex molecules. Solid-phase strategies are considered methods of election for medium-length peptide syntheses not only on the research scale but for multigram-scale production, as well....
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Tentacle‐like polymers decorated with several copies of peptide antigens can be interesting tools to increase the ability to capture circulating antibodies in patient sera, using cooperative effects for stronger avidity. We previously showed that antibodies from multiple sclerosis (MS) patient sera preferentially recognize hyperglucosylated adhesin...
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Immune response to biologics treatment, while widely reported, yet fails to correlate with clinical outcomes and assay to assay comparison is often not possible. Hence, we developed a new peptide based-detection assay to stratify pediatric patients with juvenile idiopathic arthritis (JIA) or chronic non-infectious uveitis (CNU) and monitor anti-dru...
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Diagnosis of Latent Autoimmune Diabetes in Adults (LADA) is based on the adult-age, anti-islet autoantibodies, and temporary insulin-independence. As in Type-1-Diabetes (T1DM), autoimmunity may trigger LADA and enteroviruses-infections can play a role. Anti-human Glutamic-Acid-Decarboxylase (hGAD) autoantibodies are accepted clinical biomarkers, bu...
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Collagen fibres degradation is a complex process involving a variety of enzymes. Fibrillar collagens, namely type I, II, and III, are the most widely spread collagens in human body, e.g., they are responsible for tissue fibrillar structure and skin elasticity. Nevertheless, the hyperactivity of fibrotic process and collagen accumulation results wit...
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Peptidomimetics play a fundamental role in drug design due to their preferential properties regarding natural peptides. In particular, compounds possessing nitrogen-containing heterocycles have been intensively studied in recent years. The triazolyl moiety incorporation decreases the molecule susceptibility to enzymatic degradation, reduction, hydr...
Article
Cosmeceutical field, which merges cosmetics and pharmaceuticals , is nowadays a highly investigated research area, because a scientific demonstration of the claimed bioactivity of new cosmeceutical ingredients is increasingly requested. In fact, an aspect differentiating traditional cosmetics from cosmeceuticals is the identification and characteri...
Article
Background Diagnosis of latent autoimmune diabetes in adults (LADA) is usually based on the adult age, islet antibody detection, and insulin independence. This study investigates the diagnostic value of antibodies against glutamic acid decarboxylase (GAD) peptides in LADA and type 1 diabetes mellitus (T1DM) patients, and their cross-reactivity with...
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We investigated several strategies, based on the use of microwave-assisted solid-phase peptide synthesis (MW-SPPS) and scalable to kilogram-scale manufacturing, for the preparation of Eptifibatide, a disulfide-bridged cyclo-heptapeptide drug approved as an antithrombotic agent. Following the very fast microwave-assisted Fmoc/tBu synthesis of the li...
Article
Recently, several peptides are used as active ingredients in topical cosmetic formulations, few information are available on their dermal stability against proteases. In this study, it was developed a simple and reliable assay to evaluate the stability of cosmeceutical peptides in skin homogenates. The quantification of studied peptides was perform...
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Among the many aspects that contribute to the wellness of each individual, healthy and younger-looking skin play a relevant role, as clearly shown by the important growth of the skin-care products market observed in recent years. In this scenario, the field of cosmeceuticals appears particularly promising, being based on cosmetic products containin...
Article
Multiple sclerosis (MS) in a multifactorial autoimmune disease in which reliable biomarkers are needed for therapeutic monitoring and diagnosis. Autoantibodies (autoAbs) are known biomarker candidates although their detection in biological fluids requires a thorough characterization of their associated antigens. Over the past twenty years, a revers...
Article
Peptides mimicking antigenic epitopes targeted by antibodies can be powerful tools to be used as antigen surrogates for the specific diagnosis and treatment of autoimmune diseases. Obtaining structural insights about the nature of peptide–antibody interaction in complex mixtures such as sera is a critical goal. In multiple sclerosis (MS), we previo...
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Diagnostics of Multiple Sclerosis (MS) are essentially based on the gold standard magnetic resonance imaging. Few alternative simple assays are available to follow up disease activity. Considering that the disease can remain elusive for years, identification of antibodies fluctuating in biological fluids as relevant biomarkers of immune response is...
Article
The development of conformationally constrained analogues of bioactive peptides is a relevant goal in peptide medicinal chemistry. Among the several classes of conformationally constrained peptides, the so‐called stapled peptides, which bear a side‐chain‐to‐side‐chain bridge, are particularly interesting since they offer the possibility to stabiliz...
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We report herein a novel ChemMatrix® Rink resin functionalised with two phenylboronate (PhB) moieties linked on the N-α and N-ε amino functions of a lysine residue to specifically capture deoxyfructosylated peptides, compared to differently glycosylated peptides in complex mixtures. The new PhB-Lys(PhB)-ChemMatrix® Rink resin allows for exploitatio...
Article
Psoriatic disease is a chronic inflammatory syndrome characterized by skin, joint, and spine involvement leading to abnormal keratinocyte proliferation and/or arthritis with enthesitis (1, 2). The immune response against self‐DNA is thought to be central in psoriasis (PsO) pathogenesis (3, 4), while less clear are the mechanisms of the eventual dev...
Article
Glycosylation has a strong impact on the chemical and physical properties of proteins and on their activity. The heterogeneous nature of this modification complicates the elucidation of the role of each glycan, thus slowing down the progress in glycobiology. Nevertheless, the great advances recently made in protein engineering and in the chemical s...
Article
The study of the process of HIV entry into the host cell and the creation of biomimetic nanosystems that are able to selectively bind viral particles and proteins is a high priority research area for the development of novel diagnostic tools and treatment of HIV infection. Recently, we described multilayer nanoparticles (nanotraps) with heparin sur...
Chapter
Deiminated proteins are the target of diagnostic anti-citrullinated peptide/protein autoantibodies (ACPA) in rheumatoid arthritis (RA). Deiminated histone H4 contained in the neutrophil extracellular traps reacts with ACPA, becoming an interesting diagnostic antigen for RA. The identification of the ACPA binding site in histone H4 was performed exp...
Article
A side effect of diabetes is formation of glycated proteins and, from them, production of advanced early glycation end products that could determine aberrant immune responses at the systemic level. We investigated a relevant aberrant post-translational modification (PTM) in diabetes based on synthetic peptides modified on the lysine side chain resi...
Article
Investigation of the role of saccharides and glycoconjugates in mechanisms of immune-mediated physiological and pathological conditions is a hot topic. In fact, in many autoimmune diseases cross-reactivity between sugar moieties exposed on exogenous pathogens and self-molecules has long been hinted. Several peptides have been reported as mimetics o...
Article
Reliable monitoring of clinical relevant anti-drug antibodies is fundamental in the follow-up of patients under adalimumab treatment. The aim of this study is to compare anti-adalimumab antibodies by using three methods based on different technologies. A cross-sectional study was performed in 50 patients with rheumatoid arthritis (RA) treated with...
Article
Over the past decades, membranotropic peptides such as positively charged cell-penetrating peptides (CPPs) or amphipathic antimicrobial peptides (AMPs) have received increasing interest in order to improve therapeutic agent cellular uptake. As far as we are concerned, we were interested in studying HCV fusion peptides as putative anchors. Two pepti...
Article
Background: Mitochondria play a role in type 1 diabetes (T1D) particularly in the treatment and prevention of disorder consequences. Due to their demonstrated role in diabetes machinery, mitochondrial proteins can be an interesting starting point to study candidate antigens in T1D. We investigated the role of relevant post-translational modificati...
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The pharmacological modulation of collagen turnover is a strategy potentially useful in different skin conditions. The serine protease inhibitor Serpin A1 and portions of its C‐terminal region have been investigated as collagen modulators. To clarify the mechanisms by which the C‐terminal 409‐418 peptide SA1‐III increases extracellular type I colla...
Article
The long lasting impetus to design novel modes of macrocyclization, and their implementation into a wide range of bioactive peptides, originates from their contributions to the restriction of conformational space and the stabilization of preferential bioactive conformations that support higher efficacy and binding affinity to cognate macromolecular...
Article
Adalimumab is a TNF-α blocker antibody similar in structure and function to natural human IgG1. Even if adalimumab is fully humanized, the development of anti-drug antibodies has been reported in several inflammatory conditions. The objective of our study was to assess the presence of anti-adalimumab antibodies (AAA) and their clinical relevance in...
Article
Somatostatin (SS) is a cyclic tetradecapeptide able to inhibit the release of growth hormone (GH) mainly through the binding to two G‐protein coupled receptor (GPCR) subtypes, SSTR2 and SSTR5. These receptors are overexpressed in approximately 90% of carcinoid tumors. However, the clinical use of somatostatin is limited by its short half‐life in vi...
Article
The design of molecules mimicking biologically relevant glycans is a significant goal for understanding important biological processesand may lead to new therapeutic and diagnostic agents. We focused our attention on the trisaccharide human natural killer cell-1 (HNK-1), considered the antigenic determinant ofmyelin-associated glycoprotein and the...
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Scientific Reports 6 : Article number: 39430; 10.1038/srep39430 published online: 23 December 2016 ; updated: 22 March 2017 . The original version of this Article contained typographical errors in the Abstract.
Article
This work describes the synthesis of thirteen cyclooctapeptides dicarba-analogues of Somatostatin, containing l- or d-allylglycine (Agl) residues at the termini of the peptide chain, through on resin Ring Closing Metathesis (RCM) of the linear octapeptides. We investigated the influence of the stereochemistry of some strategic amino acids on the pr...
Article
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In autoimmune diseases, there have been proposals that exogenous “molecular triggers”, i.e., specific this should be ‘non-self antigens’ accompanying infectious agents, might disrupt control of the adaptive immune system resulting in serious pathologies. The etiology of the multiple sclerosis (MS) remains unclear. However, epidemiologic data sugges...
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Background The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of systemic lupus erythematosus (SLE) patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (Crithidia Luciliae immunofluorescence test (CLIFT)). To overcome the limits of CLIFT and soli...
Article
Antibodies, induced during infections or in autoimmune diseases, exert their protective or destructive effects as part of an orchestrated system that contains several other immune system related proteins and cells. Accordingly immunological assessment of the humoral immune response should include not only the determination of antigen specific antib...
Article
Background The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of SLE patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (CLIF test). Objectives To overcome the limits of CLIFT and solid phase chromatin assays, we explored the diagnostic potenti...
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Our study tested the hypothesis that immunoglobulins differ in their ability to activate the nuclear factor-κB pathway mediated cellular responses. These responses are modulated by several properties of the immune complex, including the ratio of antibody isotypes binding to antigen. Immunoassays allow the measurement of antigen specific antibodies...
Article
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Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recr...
Data
Effect of SNP rs1143679 genotype on dsDNA specific antibody level ratios. Binding of IgG and IgM to dsDNA was determined by functional antibody profiling analysis. Individuals within the study groups were classified based on their genotype. Boxes show interquartile ranges, horizontal lines stand for median. Asterisks indicate statistically signific...
Data
Complement C4 deposition on nucleic-acid-containing and protein antigens. Scatterplots show the relationship between IgG reactivity and C4 fixation in the sera of healthy (blue), DC (green) and SLE (red) subjects. Numbers indicate percentage of SLE subjects in the respective quadrants, which were generated by 98th percentile boundaries of the NHS g...
Article
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The aim of this study was to provide proof-of-concept for quantitative and qualitative label-free detection of immune complexes through myeloid cells with imaging surface plasmon resonance. Surface plasmon resonance imaging was first applied to monitor the binding of human sera from healthy and RA patients to immobilised citrullinated RA specific p...
Article
Introduction: New low-cost strategies and enhancement of the already described methods to manufacture peptide molecules on an industrial scale are highly requested, particularly for peptides such as octreotide, which, along with goserelin and leuprolide, dominate the global peptide market. A number of patents related to the production of octreotid...
Article
Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudde...
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The role of pathologic auto-antibodies against myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis is a highly controversial matter. As the use of animal models may enable to unravel the molecular mechanisms of the human disorder, numerous studies on multiple sclerosis are carried out using experimental autoimmune encephalomyelitis (EAE...
Article
The Nucleocapsid protein NCp7 (NC) is a nucleic acid chaperone responsible for essential steps of the HIV-1 life cycle and an attractive candidate for drug development. NC destabilizes nucleic acid structures and promotes the formation of annealed substrates for HIV-1 reverse transcription elongation. Short helical nucleic acid segments bordered by...
Article
The modulation of collagen turnover can be a relevant pharmacological target in the context of treating either pathological or pathophysiological conditions, such as collagen-related diseases and skin aging. Our recent work has focused on the search for short-chain peptides as lead compounds for further development of compounds that enhance the pro...
Article
Lipoic acid is a heterocyclic sulfur-containing derivative of octanoic acid that is characterized by a 1,2-dithiolane ring. Found in nature as an essential protein cofactor, lipoic acid is implicated in cellular metabolic reactions. In particular, lipoylation is an essential posttranslational modification involved in cellular energetic metabolism p...
Article
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The interaction of lipid environments with the type I' β-turn peptide structure called CSF114 and its N-glucosylated form CSF114(Glc), previously developed as a synthetic antigenic probe recognizing specific autoantibodies in a subpopulation of multiple sclerosis patients' serum, was investigated by fluorescence spectroscopy and electrochemical exp...
Article
Primary Biliary Cirrhosis is an immune-mediated chronic liver disease whose diagnosis relies on the detection of serum anti-mitochondrial antibodies directed against a complex set of proteins, among which pyruvate dehydrogenase complex is considered the main autoantigen. We studied the immunological role of the lipoyl domain of this protein using s...