Chiara Cassiano

Chemical Proteomics Reveals Heat Shock Protein 60 To Be the Main Cellular Target of the Marine Bioactive Sesterterpene Suvanine

Marine bioactive compounds are potential drug leads because of their diverse pharmacological effects against human diseases. The identification of their cellular targets is crucial for a rational approach to their application in medicinal chemistry. Thus, we have analyzed the cell interactome of suvanine, a sulfated tricyclic terpenoid of marine origin endowed with an interesting anti‐inflammatory activity, by application of a chemical proteomic approach. Heat Shock Protein 60, a chaperone involved in the inflammatory response, is the main cellular target of suvanine, which is also able to interfere with protein chaperone activity, giving evidence for its anti‐inflammatory properties.

Identification of novel interactors of human telomeric G-quadruplex DNA

A chemoproteomic-driven approach was used to investigate the interaction network between human telomeric G-quadruplex DNA and nuclear proteins. We identified novel G-quadruplex binding partners, able to recognize these DNA structures at chromosome ends, suggesting a possible, and so far unknown, role of these proteins in telomere functions.

Heat shock proteins as key biological targets of the marine natural cyclopeptide perthamide C

Linking bioactive compounds to their cellular targets is a central challenge in chemical biology. Herein we report the mode of action of perthamide C, a natural cyclopeptide isolated from the marine sponge Theonella swinhoei. Through an emerging mass spectrometry-based chemical proteomics approach, Heat Shock Protein 90 and Glucose Regulated Protein 94 were identified as key targets of perthamide C and this evidence has been validated using surface plasmon resonance. The ability of perthamide C to influence heat shock protein-mediated cell apoptosis revealed that this marine metabolite could be a good candidate for the development of a lead compound with therapeutic applications based on apoptosis modulation.

β-Boswellic acid, a bioactive substance used in food supplements, inhibits protein synthesis by targeting the ribosomal machinery.

The Boswellia gum resin extracts have been used in traditional medicines because of their remarkable anti-inflammatory properties. Nowadays, these extracts are on the market as food supplements. β-Boswellic acid (βBA) is one of the main pentacyclic triterpene components, among the family of BAs, of the Boswellia gum resins. BAs have been broadly studied and are well known for their wide anti-inflammatory and potential anticancer properties. In this paper, a mass spectrometry-based chemoproteomic approach has been applied to characterize the whole βBA interacting profile. Among the large numbers of proteins fished out, proteasome, 14-3-3 and some ribosomal proteins were considered the most interesting targets strictly connected to the modulation of the cancer progression. In particular, because of their recent assessment as innovative chemotherapeutic targets, the ribosomal proteins were considered the most attractive βBA partners, and the biological role of their interaction with the natural compound has been evaluated. Copyright

Identification of Trombospondin-1 as a Novel Amelogenin Interactor by Functional Proteomics

Amelogenins are a set of low molecular-weight enamel proteins belonging to a group of extracellular matrix (ECM) proteins with a key role in tooth enamel development and in other regeneration processes, such as wound healing and angiogenesis. Since only few data are actually available to unravel amelogenin mechanism of action in chronic skin healing restoration, we moved to the full characterization of the human amelogenin isoform 2 interactome in the secretome and lysate of Human Umbilical Vein Endothelial cells (HUVEC), using a functional proteomic approach. Trombospondin-1 has been identified as a novel and interesting partner of human amelogenin isoform 2 and their direct binding has been validated thought biophysical orthogonal approaches.