Structure and biological activity of a conformational constrained apolipoprotein A-I-derived helical peptide targeting the protein haptoglobin (Articolo in rivista)

Type
Label
  • Structure and biological activity of a conformational constrained apolipoprotein A-I-derived helical peptide targeting the protein haptoglobin (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1039/c4ra08507h (literal)
Alternative label
  • Cigliano, Luisa; De Rosa, Lucia; Diana, Donatella; Di Stasi, Rossella; Spagnuolo, Maria Stefania; Maresca, Bernardetta; Fattorusso, Roberto; D'Andrea, Luca D. (2014)
    Structure and biological activity of a conformational constrained apolipoprotein A-I-derived helical peptide targeting the protein haptoglobin
    in RSC advances
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cigliano, Luisa; De Rosa, Lucia; Diana, Donatella; Di Stasi, Rossella; Spagnuolo, Maria Stefania; Maresca, Bernardetta; Fattorusso, Roberto; D'Andrea, Luca D. (literal)
Pagina inizio
  • 51353 (literal)
Pagina fine
  • 51361 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 4 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 9 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 93 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • University of Naples Federico II; Consiglio Nazionale delle Ricerche (CNR); Seconda Universita degli Studi di Napoli (literal)
Titolo
  • Structure and biological activity of a conformational constrained apolipoprotein A-I-derived helical peptide targeting the protein haptoglobin (literal)
Abstract
  • The development of novel pharmacological treatments for atherosclerosis is an active research field in medicinal chemistry. It has been shown that the acute phase protein haptoglobin (Hpt) plays a role in modulating the reverse cholesterol transport binding to the HDL-major protein Apolipoprotein A-I, and it also plays a role in impairing the activity of the lecithin-cholesterol acyltransferase (LCAT). We reported that the peptide P2a in vitro and in vivo restores the LCAT activity in the presence of Hpt. Now, we have designed and characterized a conformational constrained P2a analogue, ApoAib, with the intention of improving Hpt binding and metabolic stability. Using non-proteogenic aminoisobutyric acid residues, we have obtained a well folded alpha-helical peptide with high proteolytic stability in serum. It binds to Hpt, impairs haptoglobin binding to HDL, and restores LCAT activity in the presence of haptoglobin. Furthermore, an interaction analysis using NMR revealed the peptide binding site involved in haptoglobin molecular recognition. In conclusion, ApoAib represents a promising candidate to improve reverse cholesterol transport for application in cardiovascular diseases. (literal)
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