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Metals role in angiogenesis
Responsabile: Antonio Magrì, antonio.magricnr.it

Descrizione:
The determination of the exact role (s) of copper ion in angiogenesis processes, can be an essential result to design new potential therapeutic agents for different severe pathologies. This requires the understanding of the metal interaction with different angiogenic factors, and its involvement in different pathways. The research activity is focused on the synthesis and the study of some peptide fragments related to Angiogenin, VEGF, HPRG proteins and fibronectin and metal/peptide complexes study. Angiogenin is a soluble protein present in normal blood plasma, able to bind till 2. 4 copper ions per molecule, and overexpressed in patients affected by different types of cancers. We have studied the copper (II) interaction with angiogenin (entire protein) and in order to gain a better understanding the metal coordination environment in the protein, different peptide fragments have been synthesized and their copper (II) complexes characterized. VEGF165 fragments, some of which including VEGF protein? 5-? 6 loop aminoacid region and containing the overlapping VEGF binding sites to VEGFR-2, has been opportunely chosen and synthesized. These sequences include some His and VEGF-VEGFR interaction sites. VEGF165, its fragments and their metals complexes are investigated by means of molecular study and biological assay. The most striking feature of Histidine-rich glycoprotein (HRG) is its unusually high content of histidine and proline residues which are concentrated in a specific domain containing multiple conserved tandem repeats of the pentapeptide GHHPH. In this context we have synthesized and characterized these complexes with different tandem-repeat fragments. A series of single-point-mutation peptides of PHSRN sequence, which is a fibronectin recognition site of integrins, are immobilized at support surfaces for attachment cell studies. Endothelial cells attachment and interaction with the extracellular matrix (ECM) transmits signal cascades that mediate major angiogenic responses. The goal of this part of the research is to develop strategies to produce bioactive and biodegradable scaffolds. The angiogenic potential of copper ions, both alone and in combination with these peptide sequences, is going to be investigated as biomaterial support


Attori:
Antonio Magrì, antonio.magricnr.it,
Anna Maria Santoro, annamaria.santorocnr.it,
Giulia Grasso, giulia.grassoibb.cnr.it,

Parole chiave: Metals, angiogenic factors

Non disponibili.
J. Colloid Interface Sci. (2010) 341, 232-239-Dalton Trans., (2010) 10678-10684-Dalton Trans., (2010) 10678-10684
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19 Records (17 escludendo Abstract e Conferenze).
Impact factor totale: 82.035 (78.727 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 84.798 (81.234 escludendo Abstract e Conferenze).






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