Conformational Analysis of Peptides and Glycopeptides Derived from the Consensus Sequence for β-O-Glucosylation

Victor   J.   Somovilla; Nuria      Martinez-Saez; Alberto      Fernandez-Tejada; Beatriz   G.   de la Torre; David      Andreu; Jesus      Jimenez-Barbero; Juan      L. Asensio; Alberto      Avenoza; Jesus   H.   Busto; Francisco      Corzana; Jesus   M.   Peregrina

Abstract

Cys-Xxx-Ser-Xxx-Pro-Cys (Xxx= any amino acid but Pro) is the most common sequence present in naturally occurring peptides and proteins glycosylated with β-O-glucose (β-O-Glc). Taking into account the lack of studies concerning the spatial disposition of this sequence, we have synthesized and analyzed, in aqueous solution, the conformational behavior of peptides and a glycopeptide derived from the particular fragment Cys-Ala-Ser-Ser-Pro-Cys. This sequence is found in the crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Our studies, based on the use of NOESY experiments in combination with molecular dynamics (MD) simulations, indicate that for this particular fragment, initially characterized by a type I β-turn motif, the glycosylation with β-O-Glc forces the peptide backbone into an extended conformation. This conformation is stabilized by the presence of both hydrogen bonds and water pockets between the peptide and the sugar moieties.

Keywords: β-O-glucosylation, Conformational analysis, Molecular dynamics, Nuclear magnetic resonance.

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Current Topics in Medicinal Chemistry

Title:Conformational Analysis of Peptides and Glycopeptides Derived from the Consensus Sequence for β-O-Glucosylation

Volume: 14 Issue: 23

Author(s): Victor J. Somovilla, Nuria Martinez-Saez, Alberto Fernandez-Tejada, Beatriz G. de la Torre, David Andreu, Jesus Jimenez-Barbero, Juan L. Asensio, Alberto Avenoza, Jesus H. Busto, Francisco Corzana and Jesus M. Peregrina

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Keywords: β-O-glucosylation, Conformational analysis, Molecular dynamics, Nuclear magnetic resonance.

Abstract: Cys-Xxx-Ser-Xxx-Pro-Cys (Xxx= any amino acid but Pro) is the most common sequence present in naturally occurring peptides and proteins glycosylated with β-O-glucose (β-O-Glc). Taking into account the lack of studies concerning the spatial disposition of this sequence, we have synthesized and analyzed, in aqueous solution, the conformational behavior of peptides and a glycopeptide derived from the particular fragment Cys-Ala-Ser-Ser-Pro-Cys. This sequence is found in the crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Our studies, based on the use of NOESY experiments in combination with molecular dynamics (MD) simulations, indicate that for this particular fragment, initially characterized by a type I β-turn motif, the glycosylation with β-O-Glc forces the peptide backbone into an extended conformation. This conformation is stabilized by the presence of both hydrogen bonds and water pockets between the peptide and the sugar moieties.

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Somovilla J. Victor, Martinez-Saez Nuria, Fernandez-Tejada Alberto, de la Torre G. Beatriz, Andreu David, Jimenez-Barbero Jesus, L. Asensio Juan, Avenoza Alberto, Busto H. Jesus, Corzana Francisco and Peregrina M. Jesus, Conformational Analysis of Peptides and Glycopeptides Derived from the Consensus Sequence for β-O-Glucosylation, Current Topics in Medicinal Chemistry 2014; 14 (23) . https://dx.doi.org/10.2174/1568026614666141216100142

DOI https://dx.doi.org/10.2174/1568026614666141216100142	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294

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