HER2-expressing cancers currently benefit from targeted therapies, including monoclonal antibodies and antibody-drug conjugates that specifically bind to the extracellular domain of the receptor. Peptides targeting HER2 represent promising candidates for the development of alternative molecular drugs. In this study, we report a dimeric version of the previously validated A9 peptide as a ligand specifically targeting HER2. The novel A9-PEG-A9 conjugate consists of two A9 peptides whose N-terminal amino groups are linked via a polyethylene glycol chain. It was synthesized using a solvent-free protocol and validated as an improved ligand, demonstrating enhanced water solubility and increased affinity for the model receptor HER2-DIVMP, as determined by the fluorescence spectroscopy titration method.
A green synthetic protocol to add a chemical function to a fully deprotected peptide to obtain a bioactive and/or fluorescent-labeled conjugate is reported. A range of S-conjugation reactions promoted by the commercially available LTA zeolite to introduce different substituents on peptide cysteine residues has been shown to take place in the solid state or in the presence of minimal amounts of organic solvent, with yields that are comparable to those of standard solution methods. The additional advantage of the procedure consists of easing the work up, for which green solvents, such as aqueous systems, can be employed. The protocol is implemented with microwave irradiation to shorten the reaction time as dielectric heating increases the diffusion rates of the mechanically milled reactants.
The current coronavirus disease-2019 (COVID-19) pandemic is due to the novel coronavirus SARS-CoV-2. The scientific community has mounted a strong response by accelerating research and innovation, and has quickly set the foundation for understanding the molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key stage of the SARS-CoV-2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of the structural and functional data on the key actors of the replicatory machinery of SARS-CoV-2, to fill the gaps in the currently available structural data, which is mainly obtained through homology modeling. Moreover, learning from similar viruses, we collect data from the literature to reconstruct the pattern of interactions among the protein actors of the SARS-CoV-2 RNA polymerase machinery. Here, an important role is played by co-factors such as Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors that hold the entire machinery together to enhance the efficiency of RNA replication.
Here we report on the most recent updates on experimental drugs successfully employed
in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as
COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have
been reported after being treated with lopinavir/ritonavir (which is widely used to treat human
immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In
addition, remdesivir, which has been previously administered to Ebola virus patients, has also
proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine,
favipiravir and co-administered darunavir and umifenovir (in patient therapies)
were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths
ratio in the last weeks significantly increased, especially in China, it is clear that the experimental
antiviral therapy, together with the availability of intensive care unit beds in hospitals
and rigorous government control measures, all play an important role in dealing with this virus.
This also stresses the urgent need for the scientific community to devote its efforts to the
development of other more specific antiviral strategies.
The first outbreak of COVID-19 in Italy occurred during the second half of February 2020 in some areas in the North of the country. Due to the high contagiousness of the infection, further spread by asymptomatic people,
Italy has become in a few weeks the country with the greatest number of infected people in the world. The large number of severe cases among infected people in Italy led to the hospitalization of thousands of patients, with a heavy burden on the National Health Service.
Methods
We analyzed data provided daily by Italian Authorities for the period from 24 February 2020 to 30 March 2020. Considering such information, we developed a forecast model in real-time, based on the cumulative log-logistic distribution.
Results
A total of 101,739 infected individuals were confirmed until 30 March 2020, of which 14,620 recovered or discharged, and 11,591 deaths. Until the same date patients quarantined at home were 43,752, whereas hospitalized patients were 31,776, of which 3981 in intensive care. The active cases (i.e. the number of patients not yet recovered until that date) were 75,528. The forecast model estimated a number of infected persons for Italy of 234,000 about, and a duration of the epidemic of approximately 4 months.
Conclusions
One month after the first outbreaks there seemed to be the first signs of a decrease in the number of infections, showing that we could be now facing the descending phase of the epidemic. The forecast obtained thanks to our model could be used by decision-makers to implement coordinative and collaborative efforts in order to control the epidemic.
The pandemic due to novel Coronavirus must be a warning for all countries worldwide, regarding a rapid and complete dissemination of information, surveillance, health organization, and cooperation among the states.
OBJECTIVE: The aim of this study was to differentiate benign from malignant adrenal tumors using positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with unilateral adrenal masses originally detected by CT or MR imaging. CONCLUSION: PET imaging with FDG can metabolically characterize adrenal masses. Abnormally increased FDG uptake in adrenal malignancies allows one to differentiate these abnormalities from benign lesions. Whole-body PET can also reveal extraadrenal tumor sites in patients with malignant tumors, using a single imaging technique for accurate disease staging.
Several different procedures are available for the immobilization of proteins on solid supports, as many advantages derive from this approach, such as the possibility to develop new protein solid-state assays. Enzymes that are anchored on gold surfaces can interact with several different molecules in a tag-free environment, opening the way to surface plasmon resonance (SPR) investigations. Nevertheless, it is often important to know the identity of the affinity-retained analyte, and mass spectrometric analysis, via its unique molecular mass identification, represents a very valuable complementary method. There are many pieces of evidence to suggest that matrix metalloproteinases (MMPs) are involved in normal and pathological processes, including embryogenesis, wound healing, inflammation, arthritis and cancer, but presumably also exhibiting other functions. The search for new inhibitors of MMI's has prompted research towards the development of new solid-state assays for the rapid evaluation of NIMP activity. We have already reported the possibility of measuring the activity of NIMP-1 anchored on solid support by coupling SPR with ESI-MS analysis. In this work, we show the in situ atmospheric pressure (AP) MALDI-MS characterization of MMPs anchored on a gold chip with known surface coverage. The study extends the MS analysis to different proteins, and sequence coverage is reported for different digestion and MS procedures. Copyright (c) 2006 John Wiley & Sons, Ltd.
Grasso G, Fragai M, Rizzarelli E, Spoto G, Yeo KJ
J Mass Spectrom (ISSN: 1076-5174, 1096-9888), 2006 Dec; 41(12): 1561-1569
The specificity of interactions between pairs of molecules cannot be explicitly given by experimental transport coefficients such as intra- or mutual diffusion coefficients. But a microscopic interpretation of the transport properties exists, where distinct diffusion coefficients (DDCs) are related to preferential, correlated motion among distinct molecules. Since in general the DDCs do not play the role of an indicator for molecular self-association phenomena if not compared with some appropriate standard, here we propose DDCs of hard spheres at the second order of volume fraction as new standard coefficients. The analysis based on these novel DDCs is designed to study intermolecular interaction between macromolecule and solvent. Comparisons of the novel non-ideal with previous ideal reference states were done, and their combined use is shown to reinforce information conveyed by the usual velocity correlation analysis. The comparison of novel hard sphere standards with real DDCs, corresponding to an homologous chemical series of poly(ethylene glycol)-water mixtures, provides a look at this polymer-solvent mixture in a dilute and semi-dilute regime.
L'Istituto di Biostrutture e Bioimmagini (IBB) del Consiglio Nazionale delle Ricerche (CNR) ha 100 unità di personale distribuite nelle sedi di Napoli e Torino (70 ricercatori/tecnologi) e svolge attività di ricerca traslazionale per lo sviluppo nuovi strumenti per la prevenzione, la diagnosi e terapie a bersaglio molecolare.
Per realizzare questi obiettivi ricercatori che studiano le biomolecole da un punto di vista strutturale e funzionale collaborano con esperti di imaging preclinico che studiano modelli cellulari ed animali di malattie umane e ricercatori clinici che effettuano sperimentazioni nell'uomo.
Le attività di ricerca comprendono la ricerca di base, un laboratorio per l’Imaging preclinico dei piccoli animali da laboratorio ed aree di ricerca clinica svolte in collaborazione con Università ed altri enti di ricerca. La combinazione di competenze inerenti la chimica teorica e la progettazione e la sperimentazione, sia in vitro che in vivo, di nuovi agenti diagnostici e terapeutici con le competenze in molteplici modalità di imaging (tra cui MRI, imaging ottico, PET / SPECT, ecografia, TC) forniscono le basi interdisciplinari per realizzare una ricerca innovativa nel campo dell'imaging molecolare e della terapia personalizzata.
Un altro settore di ricerca sviluppato dall’IBB è rappresentato dall’e-Health. L’attività ha lo scopo di realizzare sistemi software open-source, costituiti da modelli, servizi e strumenti di supporto alla diagnosi, terapia e follow-up, nonché per la gestione innovativa dei processi sanitari.
L'Istituto fa parte del nodo italiano del Forum strategico europeo sulle infrastrutture di ricerca denominato EuroBioimaging (EuBi). EuBi è una large-scale facility a livello pan-europeo in grado di fornire a ricercatori provenienti da tutta Europa il libero accesso alle più innovative tecnologie di imaging biologico e medicale.
L’attività fondamentale dell’Istituto di Biostrutture e Bioimmagini è costituita dalle seguenti aree di ricerca:
• Design, sintesi, espressione e caratterizzazione strutturale di molecole di interesse biologico, e loro interazioni con ioni metallici. Applicazioni in campo diagnostico e terapeutico.
• Tecnologie biochimiche e biostrutture;
• Tecnologie biochimiche finalizzate alla diagnostica per immagini;
• Diagnostica per immagini e radioterapia;
• Imaging molecolare preclinico e clinico. Nuovi agenti diagnostici/teragnostici per Imaging Molecolare;
• Sviluppo di soluzioni tecnologiche innovative di e-health, con particolare attenzione alla tematiche della telemedicina e della diagnosi assistita.