Pyrazolo-isothiazole dioxide: an interesting scaffold for the preparation of peptidomimetics

There are many examples in literature of peptidomimetics that incorporate a heterocycle scaffold into a peptide, or a peptide-like sequence. The pre-organization of peptide shape, via the introduction of a structural heterocyclic motif that imparts conformational restriction, can enhance binding and hence therapeutic potential.1 Hitherto the standard approach to combine heterocycles and peptides has been to functionalize the side chain or the N/C termini of an amino acid building block with the heterocyclic moiety.2 A few examples have been accomplished in which the heterocycles are part of the peptide backbone itself.3 By the way of a 1,3-dipolar cycloaddition reaction between diazoacetates 2 and the high reactive double bond of the 3-amino isothiazole dioxide partner 1, the adducts 3 are obtained in high yield and complete regioselectivity. The presence in compounds 3 of the carboxylic substituent and the pyrazole NH group can be exploited for coupling reaction with amino acids. By this way a peptide sequence can be generated characterized by the rigid planar geometry of the heterocyclic system favoring a particular orientation of the growing peptide chain (Figure). Moreover the presence of the sulfonyl group as well as the NH group at C-3 is of interest. They can behave as hydrogen bond acceptor and donor, respectively, giving raise to interactions with proteins or other potential targets. The synthesis of model peptidomimetics containing the heterocyclic scaffold, NMR analyses and computational studies are reported

Nanofibers from small molecules

Electrospinning is a simple and versatile technique used for the fabrication of continuous micro and nanofibers. This approach is inexpensive, scalable, reliable and mainly used from polymer solutions and polymer melts. Recent studies have demonstrated that high molar mass polymers are not essential for production of uniform electrospun fibers but that sufficient intermolecular interactions acting as chain entanglements is the primary criterion.[2] A study on the electrospinnability of non natural small molecules is here reported for the first time

Peptidomimetics based on electrospun nanofibers

Electrospinning is a simple and versatile technique used for the fabrication of continuous micro and nanofibers. This approach is inexpensive, scalable, reliable and mainly used from polymer solutions and polymer melts. Recent studies have demonstrated that high molar mass polymers are not essential for production of uniform electrospun fibers but that sufficient intermolecular interactions acting as chain entanglements is the primary criterion. A study on the electrospinnability of short peptide chains containing natural amino acids (Gly, Ala, Leu, Val) together with a heterocyclic scaffold properly functionalized, is here reported

Bioglio - Veglio - Mosso Santa Maria - Quittengo - Campiglia Cervo - Valle Mosso - Valle San Nicolao - Camandona, località Alta Valsessera. Attività di ricognizione con individuazione di siti preistorici e altomedievali

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Bioglio - Veglio - Mosso Santa Maria - Quittengo - Campiglia Cervo - Valle Mosso - Valle San Nicolao - Camandona, località Alta Valsessera. Attività di ricognizione con individuazione di siti preistorici e altomedievali

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Rationale and protocol of RESORT, a randomized, open-label, multicenter phase II study to evaluate the efficacy of sorafenib in patients with advanced renal cell carcinoma after radical resection of the metastases

The introduction of targeted agents did not totally resolve the approach to the treatment of metastatic renal cell carcinoma (mRCC) because complete response is rarely achieved. Recent findings seem to indicate that metastasectomy may improve survival. The RESORT study was designed to evaluate the additional clinical benefit of metastasectomy followed by sorafenib in a population of mRCC patients. With the aim of evaluating time to recurrence, 132 patients with mRCC who underwent radical resection of metastases at the time of recurrence after nephrectomy will be randomized to receive either sorafenib or best supportive care. Targeted treatment will be administered for up to 52 weeks or discontinued in the case of disease recurrence or unacceptable toxicity. Patients will be followed for a period of 36 months