Conformationally restricted PACAP27 analogues incorporating type II/II′ IBTM β-turn mimetics. Synthesis, NMR structure determination, and binding affinity

Rosario González-Muñiz, Mercedes Martín-Martínez, Cesare Granata, Eliandre De Oliveira, Clara M. Santiveri, Carlos González, Diana Frechilla, M. Teresa García-López, Joaquín Del Río, M. Teresa García-López, M. Angeles Angeles Jiménez, David Andreu

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10 Citations (Scopus)


To probe the importance of a proposed β-turn within residues S9-R12 of PACAP for recognition by VIP/PACAP receptors, compounds 1 and 2, two conformationally restricted analogues of PACAP27 incorporating respectively (S)- or (R)-IBTM as type II or II′ β-turn dipeptide mimetic at the Y10-S11 position, were synthesized. According to 1H NMR conformational analyses in aqueous solution and 30% TFE, both PACAP27 and the [S-IBTM10,11]PACAP27 analogue 1 adopt similar ordered structures. PACAP27 shows an N-terminal disordered region (residues H1-F6) and an α-helical conformation within segment T7-L27. For residues S9-R12, our data seem more compatible with a segment of the α-helix than with the β-turn previously proposed for this fragment. In compound 1 the α-helix, also spanning T7-L27 residues, appears slightly distorted at the N-terminus relative to the native peptide. Although this distortion could lead to the marked decrease in binding affinity of this compound at the VIP/PACAP receptors, the lack of the Y10 side chain in analogues 1 and 2 could also significantly affect the binding of these compounds.

Original languageEnglish
Pages (from-to)3173-3183
Number of pages11
JournalBioorganic & Medicinal Chemistry
Issue number12
Publication statusPublished - Dec 2001
Externally publishedYes

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