A5032998349- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Mitochondrial Function and Pathology
- Angiogenesis and VEGF in Cancer
- Iron Metabolism and Disorders
- Advanced biosensing and bioanalysis techniques
- Genomics and Phylogenetic Studies
- Nanoparticle-Based Drug Delivery
- Hemoglobin structure and function
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Cell Adhesion Molecules Research
- Transgenic Plants and Applications
- Computational Drug Discovery Methods
- Protein purification and stability
- Amino Acid Enzymes and Metabolism
- Pharmacological Receptor Mechanisms and Effects
- Ubiquitin and proteasome pathways
- Sirtuins and Resveratrol in Medicine
- Toxin Mechanisms and Immunotoxins
National Research Council
2015-2024
Institute of Molecular Biology and Pathology
2015-2024
Sapienza University of Rome
1995-2022
National Academies of Sciences, Engineering, and Medicine
2008-2014
Istituto Pasteur
2003-2007
Institut Pasteur
2005
MRC Laboratory of Molecular Biology
2000-2003
IRBM Science Park
1997-2000
University of Chieti-Pescara
1998-2000
Medical Research Council
2000
A novel antibody–drug conjugate (ADC) was synthesized incorporating ferritin-based nanoparticles. An average of three molecules monoclonal antibody (mAb) Ep1 to the human melanoma-specific antigen CSPG4 were conjugated a single ferritin cage encapsulating about 50 cisplatin (HFt–Pt–Ep1). The HFt–Pt–Ep1 nanoparticle had an estimated molecular size 900 kD and 33 nm, flow cytometry demonstrated specific binding CSPG4+ melanoma cell line, but not CSPG4− breast carcinoma line. As compared...
A novel human ferritin-based nanocarrier, composed of 24 modified monomers able to auto-assemble into a protein cage, was produced and used as selective carrier anti-tumor payloads. Each monomer derives from the genetic fusion two distinct modules, namely heavy chain ferritin (HFt) stabilizing/protective PAS polypeptide sequence rich in proline (P), serine (S), alanine (A) residues. Two genetically fused constructs containing polymers with 40- 75-residue lengths, respectively, were compared....
This report describes the assessment of homology-based predictions submitted to fifth edition Critical Assessment Methods for Protein Structure Prediction (CASP5) experiment. We assessed ability methods predict overall fold, portions structure that differ substantially between target protein and its closest structural homologue conformation side-chains. also compared results with those obtained in previous editions experiment derived some general conclusions about state art comparative...
We describe here the results of our analysis comparative modeling predictions submitted to fourth round Critical Assessment Structure Prediction (CASP4). On basis a numerical evaluation models, we assessed their ability predict overall fold correctly, relative orientation domains in multidomain proteins, conformation side chains, loop regions, and biologically important residues targets. also discuss performance automatic prediction servers compare CASP4 with those obtained CASP3. Proteins...
Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor for several factors of the VEGF family. Endothelial cells express membrane-spanning form VEGFR-1 and secrete soluble variant comprising only extracellular region. The role this has not yet been completely defined. In study, we report that secreted present within matrix deposited by in culture, suggesting possible involvement cell adhesion migration. assays, region specifically promoted attachment....
Nanoparticle-based systems are promising for the development of imaging and therapeutic agents. The main advantage nanoparticles over traditional lies in possibility loading multiple functionalities onto a single molecule, which useful and/or diagnostic purposes. These include targeting moieties able to recognize receptors overexpressed by specific cells tissues. However, targeted delivery requires an accurate system design. We present here rationally designed, genetically engineered,...
The genetic and epigenetic factors underlying the variable penetrance of homoplasmic mitochondrial DNA mutations are poorly understood. We investigated a 16-year-old patient with hypertrophic cardiomyopathy harboring m.4277T>C mutation in mt-tRNA(Ile) (MTTI) gene. Skeletal muscle showed multiple respiratory chain enzyme abnormalities decreased steady-state level mutated mt-tRNA(Ile). Transmitochondrial cybrids grown on galactose medium demonstrated functional effect this cell viability,...
Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% located transfer RNA (tRNA) genes and responsible for a wide range of syndromes, which no effective treatment is available at present. We show that three human mt aminoacyl-tRNA syntethases, namely leucyl-, valyl-, isoleucyl-tRNA synthetase able improve both viability bioenergetic proficiency transmitochondrial cybrid cells carrying pathogenic mt-tRNA(Ile) gene....
The group II truncated hemoglobin from Bacillus subtilis has been cloned, expressed, purified, and characterized. B. is a monomeric protein endowed with an unusually high oxygen affinity (in the nanomolar range) such that apparent thermodynamic binding constant for O2 exceeds CO by 1 order of magnitude. kinetic 2basis resides mainly in very slow rate ligand release. extremely stable ferrous oxygenated adduct resistant to oxidation, which can be achieved only oxidant large excess, e.g....
Summary Plants are promising hosts for the production of monoclonal antibodies (mAbs). However, proteolytic degradation produced both in stable transgenic plants and using transient expression systems is still a major issue efficient high‐yield recombinant protein accumulation. In this work, we have performed detailed study profiles two human IgG1 mAbs plants: an anti‐HIV mAb 2G12 tumour‐targeting H10. Even though they use different light chains (κ λ, respectively), fragmentation pattern was...
Ferritin receptor (CD71) is an example of a very attractive cancer target, since it highly expressed in virtually all tumor types, including metastatic loci. However, this target can be considered to inaccessible conventional therapies, due its presence many healthy tissues. Here, we describe the preclinical evaluation proteases-activatable human ferritin (HFt)-based drug carrier (The-0504) that able selectively deliver wide-spectrum topoisomerase I inhibitor Genz-644282 CD71-expressing...
The gene coding for a hemoglobin‐like protein (Tf‐trHb) has been identified in the thermophilic actinobacterium Thermobifida fusca and cloned Escherichia coli overexpression. crystal structure of ferric, acetate‐bound derivative, was obtained at 2.48 Å resolution. three‐dimensional Tf‐trHb is similar to structures reported truncated hemoglobins from Mycobacterium tuberculosis Bacillus subtilis its central domain. complete lack diffraction patterns relative N‐ C‐terminal segments indicates...
Understanding the role of partially folded intermediate states in folding mechanism a protein is crucial yet very difficult problem. We exploited kinetic approach to demonstrate that transient thermostable member widely studied cytochrome c family (cytochrome 552 from Thermus thermophilus) indeed on-pathway. This first clear indication an obligatory c. The fluorescence properties this relative position heme and only tryptophan residue cannot correspond their native orientation. Based on...
Serine hydroxymethyltransferase is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the interconversion of serine and glycine using tetrahydropteroylglutamate as one-carbon carrier. In all phosphate-dependent enzymes, amino acid substrates are bound released through transaldimination process, in which an internal aldimine external interconverted via gem-diamine intermediates. Bioinformatic analyses sequences structures showed presence two highly conserved residues, tyrosine arginine,...