Synthesis and conformational analysis of three cyclic hexapeptides cyclo(‐Gly1‐Pro2‐Phe3‐Val4‐Xra5‐Phe6), Xaa= Phe (I), D‐Phe (II) and D‐Pro (III), were carried out to examine the influence of proline on the formation of reverse turns and the dynamics of hydrophobic peptide regions. Assignment of all 1H and 13C resonances was achieved by homo‐ and heteronuclear 2D‐NMR techniques (TOCSY, ROESY, HMQC, HMQC‐TOCSY and HMBCS‐270). The conformational analysis is based on interproton distances derived from ROESY spectra and homo‐ and heteronuclear coupling constants (E.COSY, HETLOC and HMBCS‐270). For structural refinements restrained molecular dynamics (MD) simulations in vacuo and in DMSO were performed. Each peptide exhibits two conformations in DMSO solution due to cis‐trans isomerism about the Gly‐Pro peptide bond. Surprisingly the cis‐Gly‐Pro segment in the minor isomers is not involved in a βVI‐turn, but forms a turn structure with cis‐Gly‐Pro in the i and i+ 1 positions. Although no stabilizing hydrogen bond is found in this turn, the φ and ψ‐angles closely correspond to a βI‐turn [Pro2:φ(i+ 1) ‐60°, ψ(i+ 1) ‐30° Phe3: φ(i+ 2) ‐100°, ψ(i+ 2) ‐50°]. Hence we call this structural element a pseudo‐βI‐turn. As expected, in the dominating all‐trans isomers proline occupies the i+ 1 position of a standard βI‐turn. Therefore, cis‐trans isomerization of the Gly1‐Pro2 amide bond only induces a local conformational rearrangement, with minor structural changes in other parts of the molecule. However, the geometry of the other regions is affected by the chirality of the i+ 1 amino acid for both isomers (βI for Phe5, βII′ for D‐Phe5 or D‐Prp5). Copyright © 1994, Wiley Blackwell. All rights reserved
The pseudo‐βI‐turn: A new structural motif with a cis peptide bond in cyclic hexapeptides
ISERNIA, Carla;
1994
Abstract
Synthesis and conformational analysis of three cyclic hexapeptides cyclo(‐Gly1‐Pro2‐Phe3‐Val4‐Xra5‐Phe6), Xaa= Phe (I), D‐Phe (II) and D‐Pro (III), were carried out to examine the influence of proline on the formation of reverse turns and the dynamics of hydrophobic peptide regions. Assignment of all 1H and 13C resonances was achieved by homo‐ and heteronuclear 2D‐NMR techniques (TOCSY, ROESY, HMQC, HMQC‐TOCSY and HMBCS‐270). The conformational analysis is based on interproton distances derived from ROESY spectra and homo‐ and heteronuclear coupling constants (E.COSY, HETLOC and HMBCS‐270). For structural refinements restrained molecular dynamics (MD) simulations in vacuo and in DMSO were performed. Each peptide exhibits two conformations in DMSO solution due to cis‐trans isomerism about the Gly‐Pro peptide bond. Surprisingly the cis‐Gly‐Pro segment in the minor isomers is not involved in a βVI‐turn, but forms a turn structure with cis‐Gly‐Pro in the i and i+ 1 positions. Although no stabilizing hydrogen bond is found in this turn, the φ and ψ‐angles closely correspond to a βI‐turn [Pro2:φ(i+ 1) ‐60°, ψ(i+ 1) ‐30° Phe3: φ(i+ 2) ‐100°, ψ(i+ 2) ‐50°]. Hence we call this structural element a pseudo‐βI‐turn. As expected, in the dominating all‐trans isomers proline occupies the i+ 1 position of a standard βI‐turn. Therefore, cis‐trans isomerization of the Gly1‐Pro2 amide bond only induces a local conformational rearrangement, with minor structural changes in other parts of the molecule. However, the geometry of the other regions is affected by the chirality of the i+ 1 amino acid for both isomers (βI for Phe5, βII′ for D‐Phe5 or D‐Prp5). Copyright © 1994, Wiley Blackwell. All rights reservedI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
