Disruption of Protein-Protein Interfaces: In Search of New by Laura Bettinetti, Matteo Magnani (auth.), Stefano Mangani

By Laura Bettinetti, Matteo Magnani (auth.), Stefano Mangani (eds.)

"Disruption of Protein-Protein Interfaces" reports the most recent advancements and destiny views in drug discovery at protein-protein interfaces. The authors element experimental and computational instruments to take on the topic and spotlight the contribution of the Italian study group to the sector. proof exhibits that blockading or modulating protein-protein interactions may perhaps result in the improvement of necessary new medicines. for this reason, in recent times nice attempt has been devoted to unveiling the molecular information of protein-protein interfaces through structural ideas e.g. X-ray diffraction, NMR spectroscopy. This booklet, written and edited through leaders within the box, presents examples from the literature of successes and screw ups to increase drug-like molecules powerful in interacting at protein-protein interfaces.

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The characterization of such interfaces represents the true barrier to effectively understanding the structural nature of PPIs and is consequently a major obstacle for designing modulating agents that can bind to those interfaces. In general, interaction interfaces are considered to be flat and rigid; in fact, they are dynamic and can be more convoluted in solution than they appear in co-crystal structures. This complexity causes some difficulties in the selection of the suitable template conformation.

The antisense oligonucleotide is then released back into the cytosol where it is capable of inhibiting additional native mRNA molecules. In cultured cells, the uptake of antisense oligonucleotides requires transfection, infection, or electroporation protocols. In xenografts and patients, the intracellular uptake of antisense molecules is achieved after intravenous or subcutaneous administration, but the mechanism facilitating the uptake is not clear. Although the xenograft data have been encouraging, the efficacy of antisense therapies in previous clinical trials has not matched the initial expectations.

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