Development of elastin-like recombinamer films with antimicrobial activity

In the present work we explored the ABP-CM4 peptide properties from Bombyx mori for the creation of biopolymers with broad antimicrobial activity. An antimicrobial recombinant protein-based polymer (rPBP) was designed by cloning the DNA sequence coding for ABP-CM4 in frame with the N-terminus of the elastin-like recombinamer consisting of 200 repetitions of the pentamer VPAVG, here named A200. The new rPBP, named CM4-A200, was purified via a simplified nonchromatographic method, making use of the thermoresponsive behavior of the A200 polymer. ABP-CM4 peptide was also purified through the incorporation of a formic acid cleavage site between the peptide and the A200 sequence. In soluble state the antimicrobial activity of both CM4-A200 polymer and ABP-CM4 peptide was poorly effective. However, when the CM4-A200 polymer was processed into free-standing films high antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi was observed. The antimicrobial activity of CM4-A200 was dependent on the physical contact of cells with the film surface. Furthermore, CM4-A200 films did not reveal a cytotoxic effect against both normal human skin fibroblasts and human keratinocytes. Finally, we have developed an optimized ex vivo assay with pig skin demonstrating the antimicrobial properties of the CM4-A200 cast films for skin applications.

The synthesis of new 6-hydrazinopurines as potential anticancer agents

[Excerpt] Purines, such as adenine, are one of the most important naturally occurring nitrogen heterocycles and they are frequently used as bioactive agents.[1,2] The increasing number of synthetic purines reveals the great potential of these compounds as enzyme inhibitors. Protein Kinases have an important regulatory role in cell proliferation, differentiation and signalling processes. Abnormal signal transduction is responsible for devastating diseases such as cancer. All of the protein kinases identified have in common the cofactor ATP indicating that the adenine nucleus is a very important scaffold for discovery of new anti-cancer agents.[3,4] Previous work identified a modest anticancer activity in a family of 6-arylaminopurines. In the view of these results, it seemed reasonable to assume that some interesting anticancer agents might result by replacement of the phenyl group by a secondary amino group linked to the N-6 atom of the adenine moiety. (...)

Synthesis and anticancer activity of N3-substituted-6,8-diaminopurines

[Excerpt] Cancer is the second most common cause of death in developed countries appearing just after cardiovascular diseases. The treatment of cancer remains a major medical challenge and the development of new anticancer drugs is an emerging topic for the scientific community. During the past three decades several chemical classes of anticancer drugs have been identified. In particular, 2,6-diamino purines proved to be important candidates as new anti-cancer agents.