Structure and molecular modelling of protected dipeptide fragment (Boc–Phe–Leu–OBzl) of enkephalin

Abstract

The conformational characteristics of a flexible totally protected C-terminal dipeptide fragment (Boc-Phe-Leu-OBzl) of enkephalin are studied using X-ray data, molecular modelling and data retrieved from the Cambridge Structural Database. The dipeptide crystallizes with seven conformers in the asymmetric unit. C(27)H(36)N(2)O(5), T = 133 K, monoclinic, P2(1), a = 13.706 (3), b = 22.800 (3), c = 30.674 (5) Å, beta = 97.15 (3) degrees, V = 9511 (3) Å(3), Z = 14, D(c) = 1.145 Mg m(-3). Six of the seven molecules exhibit folded conformations with hydrophobic groups disposed at the opposite side of the peptide backbone. The characteristic Phi(1) and Psi(1) angles of the Phe residue and Phi(2) of the Leu fragment are in the allowed region defined in the Ramachandran diagram. However, they do not belong to the family of the lowest energy conformations. In the crystal, molecules are interconnected via N-H.O hydrogen bonds of peptide groups forming an infinite sheet similar to a parallel beta-sheet. Molecular dynamics simulations performed in vacuo reproduce the conformers and rotamers detected in the solid state.

Crystal Structure of the N-Benzyloxycarbonyl-alanyl-phenylalanyl-methyl Ester: The Importance of the H-Bonding Pattern

“…Besides, also in this case, a similar H-bonding network implicating the amide and uretane groups was found in the solid state. This H-bonding network is also responsible for the self-assembling of Z-AF-OH in solution [23] and resembles that observed in natural β-sheet peptidic motives [5][6][7]. In both cases-the Z-AF-OH and the Z-AF-OMe compounds-the assembly can be described as a straight parallel β-sheet [25], without any twist between the backbond strands along the H-bonding direction, often found in related N-protected dipeptides [26].…”

“…In this regard, crystallographic studies on simple short peptidic sequences have shown the formation of supramolecular structures in the solid state which resemble the interaction patterns found in helices [2][3][4], sheets [5][6][7] and turns [8,9]. These structural patterns are normally stabilized by the synergic action of weak, non-covalent interactions such as H-bonds, electrostatic, aromatic face to face or edge to face and van der Waals contacts [10,11].…”

Pearls on a string: aZ′ = 7 structure for glycyl-L-valine

“…Two of these are peptides, viz. L-Met-l-Ala in space group P6 1 (Go È rbitz, 2003) and Boc-l-Phe-l-Leu-OBzl, a protected dipeptide fragment of enkephalin, in space group P2 1 (Antolic  et al, 1999). In both cases, the seven molecules exhibit a mixture of conformations, particularly with regard to the side chains, but also with extensive¯exibility for the peptide main chains.…”

Conformational change from antiparallel β‐sheet to α‐helix in a series of depsipeptide, ‐(Leu‐Leu‐Lac)n‐: Syntheses, spectroscopic studies, and crystal structures of Boc‐Leu‐Lac‐OEt and Boc‐(Leu‐Leu‐Lac)n‐OEt (n = 1, 2)

“…Therefore the solid‐state structure of 3 is relatively close to the classical model for antiparallel pleated β‐sheet except at the ester connection between Leu 13 and Lac 14 and the ψ angle of Leu 13 . Among crystal structures of oligo‐peptides, the flat and planer β‐strand is not often observed except shorter sequences, such as containing two and three residues 68, 86, 87, 89–92. Longer sequences containing four and five residues are sometimes reported 90, 93.…”

“…If the side chains do not hinder the interchain association, antiparallel sheets are more stable than parallel sheets due to their narrowly spaced NH ··· OC bond length. In the synthetic peptide β‐sheet crystals, antiparallel interactions93, 99–104 are almost dominant except for the specific cases of parallel assemblies 68, 89…”