http://www.cnr.it/ontology/cnr/individuo/prodotto/ID15715

Novel glycosylated VIP analogs: synthesis, biological activity, and metabolic stability (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

Novel glycosylated VIP analogs: synthesis, biological activity, and metabolic stability (Articolo in rivista) (literal)

Anno

2008-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1002/psc.932 (literal)

Alternative label

David Dangoor; Barbara Biondi; Marina Gobbo; Yelena Vachutinski; Mati Fridkin; Illana Gozes; Raniero Rocchi (2008)
Novel glycosylated VIP analogs: synthesis, biological activity, and metabolic stability
in Journal of peptide science (Print)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

David Dangoor; Barbara Biondi; Marina Gobbo; Yelena Vachutinski; Mati Fridkin; Illana Gozes; Raniero Rocchi (literal)

Pagina inizio

321 (literal)

Pagina fine

328 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

14 (literal)

Rivista

Journal of peptide science (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

3 (literal)

Note

Scopu (literal)
ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel; Department of Chemical Sciences, University of Padova, Institute of Biomolecular Chemistry, 1-35131 Padova, Italy (literal)

Titolo

Novel glycosylated VIP analogs: synthesis, biological activity, and metabolic stability (literal)

Abstract

Vasoactive intestinal peptide (VIP) is a prominent neuropeptide, exhibiting a wide spectrum of biological activities in mammals. However, the clinical applications of VIP are mainly hampered because of its rapid degradation in vivo. Peptide glycosylation, a procedure frequently used to increase peptide resistance to proteolytic degradation and consequently increase peptide metabolic stability, has not been performed yet on VIP. The presence of three N-glycosylation sites on VIP receptor type 1 (VPAC1) was previously demonstrated. Therefore, glycosylation of the VIP ligand could potentially increase its receptor affinity because of glyco-glyco interactions between the ligand and the receptor. In order to enhance VIP's metabolic stability and to increase its ligand-receptor binding/activation, eight glycosylated VIP derivatives were successfully synthesized by the solid-phase procedure. Each VIP analog was monoglycosylated by a monosaccharide addition to one amino-acid residue along the sequence. Glycosylation did not affect the ?-helical structure shown by the native VIP in organic environment. Few glycosylated VIP analogs displayed highly potent VPAC1 receptor binding and cAMP-induced activation; only 4-6 fold lower in comparison to the native VIP. Furthermore, the peptide analog glycosylated on Thr11 ([11Glyc]VIP) showed a significantly enhanced stability toward trypsin enzymatic degradation in comparison to VIP. Analysis of the degradation products of [11Glyc]VIP showed that differently from VIP, incubation of the peptide [11Glyc]VIP with trypsin resulted in no cleavage at the Arg12-Leu13 peptide bond, suggesting that VIP glycosylation may lead to enhanced metabolic stability. (literal)

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