A5018992013- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Peptides and Activities
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Proteoglycans and glycosaminoglycans research
- Biochemical and Structural Characterization
- Neuropeptides and Animal Physiology
- Nicotinic Acetylcholine Receptors Study
- Venomous Animal Envenomation and Studies
- Rabies epidemiology and control
- RNA Interference and Gene Delivery
- Protein Structure and Dynamics
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Nanoparticle-Based Drug Delivery
- HIV Research and Treatment
- Atomic and Molecular Physics
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Toxin Mechanisms and Immunotoxins
- Cell Adhesion Molecules Research
- Insect and Pesticide Research
- Nuclear physics research studies
- Bacillus and Francisella bacterial research
University of Siena
2016-2025
Ospedale Santa Maria alle Scotte
2020-2024
Azienda Ospedaliera Universitaria Senese
2011-2023
Toscana Life Sciences
2016-2022
Harvard University
2020
National Institutes of Health
2020
Yale University
2020
Rockefeller University
2020
University of Florence
2013
Tumour Institute of Tuscany
2013
Introduction: Antibiotic-resistant bacteria kill 25,000 people every year in the EU. Patients subject to recurrent lung infections are most vulnerable severe or even lethal infections. For these patients, pulmonary delivery of antibiotics would be advantageous, since inhalation can achieve higher concentration lungs than iv administration and provide a faster onset action. This allow for doses hence reduce number treatments required. We report here about new nanosystem (M33-NS) obtained by...
A large 10-mer phage peptide library was panned against whole Escherichia coli cells, and an antimicrobial (QEKIRVRLSA) selected. The synthesized in monomeric dendrimeric tetrabranched form (multiple antigen [MAP]), which generally allows a dramatic increase of stability to peptidases proteases. antibacterial activity the E. much higher than that form. Modification original sequence, by residue substitution or sequence shortening, produced three different MAPs, M4 (QAKIRVRLSA), M5...
Long-pentraxin 3 (PTX3) is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 comprises pentraxin-like C-terminal domain involved complement activation via C1q interaction an N-terminal extension unknown functions. binds fibroblast growth factor-2 (FGF2), inhibiting its pro-angiogenic pro-restenotic activity. Here, retroviral transduced endothelial cells (ECs) overexpressing the fragment PTX3-(1-178) showed reduced mitogenic activity...
Abstract A synthetic antimicrobial peptide was identified as a possible candidate for the development of new antibacterial drug. The peptide, SET-M33L, showed MIC 90 below 1.5 μM and 3 Pseudomonas aeruginosa Klebsiella pneumoniae , respectively. In in vivo models P. infections, its pegylated form (SET-M33L-PEG) enabled survival percentage 60–80% sepsis lung infections when injected twice i.v. at 5 mg/Kg, completely healed skin administered topically. Plasma clearance different kinetics...
Peptides derived from the sequence of a single-chain, recombinant, antiidiotypic antibody (IdAb; KT-scFv) acting as functional internal image microbicidal, wide-spectrum yeast killer toxin (KT) were synthesized and studied for their antimicrobial activity by using KT-susceptible Candida albicans model organism. A decapeptide containing first three amino acids (SAS) light chain CDR1 was selected optimized alanine replacement single residue. This peptide exerted strong candidacidal in vitro,...
We found that synthetic peptides in the form of dendrimers become resistant to proteolysis. To determine molecular basis this resistance, different bioactive were synthesized monomeric, two‐branched and tetra‐branched incubated with human plasma serum. Proteolytic resistance branched multimeric sequences was compared same as linear molecules. Unmodified cleaved detected by high pressure liquid chromatography mass spectrometry. An increase peptide copies did not sequences, whereas...
We describe the nonnatural antimicrobial peptide KKIRVRLSA (M33) and its capacity to neutralize LPS-induced cytokine release, preventing septic shock in animals infected with bacterial species of clinical interest. M33 showed strong resistance proteolytic degradation when synthesized tetrabranched form 4 peptides linked by a lysine core, making it suitable for use vivo. HPLC mass spectrometry demonstrated stability serum beyond 24 h. was found be very selective gram-negative bacteria....
The branched M33 antimicrobial peptide was previously shown to be very active against Gram-negative bacterial pathogens, including multidrug-resistant strains. In an attempt produce back-up molecules, we synthesized isomer consisting of D-aminoacids (M33-D). This isomeric version showed 4 16-fold higher activity Gram-positive Staphylococcus aureus and epidermidis, than the original peptide, while retaining strong bacteria. both peptides influenced by their differential sensitivity proteases....
Near-infrared quantum dots (NIR QDs) are a new class of fluorescent labels with excellent bioimaging features, such as high fluorescence intensity, good stability, sufficient electron density, and strong tissue-penetrating ability. For all NIR QDs have great potential for early cancer diagnosis, in vivo tumor imaging resolution microscopy studies on cells.In the present study we constructed functionalized NT4 cancer-selective tetrabranched peptides (NT4-QDs). We observed specific uptake...
Infection sustained by multidrug‐resistant and extensively drug‐resistant bacterial pathogens is often untreatable with the standard of care antibiotics, combination anti‐infective compounds represents only therapeutic strategy to face this major clinical treat. SET‐M33 a novel antimicrobial peptide (AMP) that has demonstrated in vitro vivo activity against Gram‐negative bacteria shown interesting features preclinical evaluations. Particularly, it showed efficacy number strains pathogens,...
Development of inhalable formulations for delivering peptides to the conductive airways and shielding their interactions with airway barriers, thus enhancing peptide/bacteria interactions, is an important part peptide-based drug development lung applications. Here, we report construction a biocompatible nanosystem where antimicrobial peptide SET-M33 encapsulated within polymeric nanoparticles poly(lactide-co-glycolide) (PLGA) conjugated polyethylene glycol (PEG). This system was conceived...
Abstract The irregular vasculature and high interstitial pressure of solid tumors hinder the delivery cytotoxic agents to cancer cells. As a consequence, doses chemotherapy necessary achieve complete tumor eradication are associated with unacceptably toxicities. selective thrombosis blood vessels has been postulated as an alternative avenue for combating cancer, depriving nutrients oxygen causing avalanche cell deaths. human antibody L19, specific EDB domain fibronectin, marker angiogenesis,...
Abstract Receptors for endogenous regulatory peptides, like the neuropeptide neurotensin, are overexpressed in several human cancers and can be targets peptide-mediated tumor-selective therapy. Peptides, however, have main drawback of an extremely short half-life vivo. We showed that neurotensin other when synthesized as dendrimers, retain biological activity become resistant to proteolysis. Here, we functional fragment NT(8-13) a tetrabranched form linked different units tumor therapy or...
Abstract In human brain the flavoprotein D ‐amino acid oxidase (hDAAO) is responsible for degradation of neuromodulator ‐serine, an important effector NMDA‐receptor mediated neurotransmission. Experimental evidence supports concept that ‐serine concentration increase by hDAAO inhibition may represent a valuable therapeutic approach to improve symptoms in schizophrenia patients. This study investigated effects on conformation and stability substrate (or pseudo‐substrate trifluoro‐ ‐alanine),...
The use of peptide receptors as targets for tumor-selective therapies was envisaged years ago with the findings that different endogenous regulatory peptides are overexpressed in several primary and metastatic human tumors, can be used tumor antigens. Branched retain or even increase, through multivalent binding, biological activity a very resistant to proteolysis, thus having markedly higher vivo compared corresponding monomeric peptides. Oligo-branched peptides, containing neurotensin (NT)...
Abstract The structure and the in vitro behavior of liposomes filled with cytotoxic drug doxorubicin (Doxo) functionalized on external surface a branched moiety containing four copies 8–13 neurotensin (NT) peptide is reported. new liposomes, DOPC‐NT 4 Lys(C 18 ) 2 , are obtained by co‐aggregation DOPC phospholipid synthetic amphiphilic molecule, NT which contains lysine scaffold derivatized lipophilic tetrabranched hydrophilic peptide, NT8–13, fragment well known for its ability to mimic...
Abstract Taxanes are highly effective chemotherapeutic drugs against proliferating cancer and an established option in the standard treatment of ovarian breast cancer. However, with paclitaxel is associated severe side effects, including sensory axonal neuropathy its poor solubility water complicates formulation. In this paper we report vitro vivo activity a new form paclitaxel, modified for conjugation tumor-selective tetrabranched peptide carrier (NT4). NT4 selectively targets tumor cells...