Original scientific paper

Conformational Studies in Solid State and Solution of Protected C-terminal Dipeptide Fragment (Boc-Phe-Pro-NH₂) of Morphiceptin

Biserka Kojić-Prodić ; Ruđer Bošković Institute, P.O.B. 1016, HR-10001 Zagreb, Croatia
Snježana Antolić ; Ruđer Bošković Institute, P.O.B. 1016, HR-10001 Zagreb, Croatia
Marina Kveder ; Ruđer Bošković Institute, P.O.B. 1016, HR-10001 Zagreb, Croatia
Ivanka Zigrović ; Ruđer Bošković Institute, P.O.B. 1016, HR-10001 Zagreb, Croatia
Jurka Kidrič ; National Institute of Chemistry, P.O.B. 30, 61015 Ljubljana, Slovenia
Štefica Horvat ; Ruđer Bošković Institute, P.O.B. 1016, HR-10001 Zagreb, Croatia

Abstract

The crystal structure of the protected C-terminal dipeptide fragment (Boc-Phe-Pro-NH₂) of the μ-opioid receptor highly selective agonist, morphiceptin (Tyr-Pro-Phe-Pro-NH₂), was determined; the crystals are monoclinic with space group P2₁ and unit cell dimensions: a = 11.5731(5), b = 6.4490(3), c = 15.4082(5) Å, β = 100.359(5)° and Z = 2. To examine the influence of proline on the conformation of peptide bond, the molecular conformation was studied in solid state and solution (using 1H and 13C NMR data). The X-ray analysis revealed the following conformations of peptide backbone: φ₁ = -63.2(5)°, ψ₁ = 156.1(4)°, ω₁ =-174.3(4)°, φ₂ =-66.0(5)° and ψ₂ = 152.0(4)°. The conformation of the Boc group is trans-trans. Experimental data revealed the trans conformation about the Phe-Pro amide bond, both in solid state and solution (DMSO). The possibility of cis/trans isomerization about the peptide bond (ω₁) was examined by theoretical calculations using BIOSYM software. Molecular modelling, including molecular dynamics simulations of the title dipeptide, is in favour of trans peptide bond.

Keywords

C-terminal dipeptide; cis/trans isomerization; morphiceptin; conformational analysis; X-ray structure; NMR; molecular dynamics simulations

Hrčak ID:

132162

URI

https://hrcak.srce.hr/132162

Publication date:

1.9.1999.

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