Helical peptides from VEGF and Vammin hotspots for modulating the VEGF-VEGFR interaction
The design, synthesis, conformational studies and binding affinity for VEGF receptors of a collection of linear and cyclic peptide analogues of the N-terminal α-helix fragments 13-25 of VEGF and 1-13 of Vammin are described. Linear 13(14)-mer peptides were designed with the help of an AGADIR algorit...
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Veröffentlicht in: | Organic & biomolecular chemistry 2013-03, Vol.11 (11), p.1896-1905 |
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Hauptverfasser: | , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The design, synthesis, conformational studies and binding affinity for VEGF receptors of a collection of linear and cyclic peptide analogues of the N-terminal α-helix fragments 13-25 of VEGF and 1-13 of Vammin are described. Linear 13(14)-mer peptides were designed with the help of an AGADIR algorithm and prepared following peptide solid-phase synthetic protocols. Cyclic peptide derivatives were prepared on-resin from linear precursors with conveniently located Glu and Lys residues, by the formation of amide linkages. Conformational analysis, CD and NMR, showed that most synthesized peptides have a clear tendency to be structured as α-helices in solution. Some of the peptides were able to bind a VEGFR-1 receptor with moderate affinity. In addition to the described key residues (Phe17, Tyr21 and Tyr25), Val14 and Val20 seem to be relevant for affinity. |
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ISSN: | 1477-0520 1477-0539 |
DOI: | 10.1039/c3ob27312a |