β‐Turns induced in bradykinin by (S)‐α‐methylproline

Abstract

The ability of (S).g-methylprolin¢ (g-MePro) to stabilis¢ reversequrn conformations in the peptlde hormone brad~/kinin (BK = Argt-Pro:-ProLGly 4-PheS-Ser6-ProLPhe~-Arg ~) has been investigated. Two BK analogues containing ,)-MePro at position 3 or position 7 were synthesised and their conformations in aqueous solution investigated by NMR spectroscopy. Whereas BK is largely disordered on the NMR time scale both analogues showed ROE connectivities in 2D-ROESY spectra indicative of reverse-turn conformations at both Pro2-Phe ~ and Ser~-Arg °. whose formation appears to be cooperative. Some potential applications of ~z-McPro as a reverse-turn mimetic in the construction of synthetic peptide libraries is discussed.

Cα‐Methyl proline: A unique example of split personality

“…L-(aMe)Pro, incorporated in a peptide antigen, 22,23 or at position 3 or 7 of the nonapeptide hormone bradykinin, [24][25][26] or in the NPNA-repeat motif of the Plasmodium falciparium protein, 27,28 was shown by 2D-NMR experiments to strongly stabilize b-turn conformations. Similar results [b-turn formation and trans L-Xxx-L-(aMe)Pro peptide bonds] were reported for L-(aMe)Pro-containing analogues of an antigen mimotope peptide 29 and the antimicrobial peptide buforin 2.…”

Synthesis and NMR Spectroscopic Characterization of Organometallics in the Laboratory of Wolfgang von Philipsborn: Reminiscences of Former Graduate Students

“…John Robinson's project comprised the specific incorporation of 13 C and 15 N markers into bradykinin analogues through chemical synthesis followed by isotope-edited ROESY spectroscopic analysis. [23] The system was ideally suited to test our new triple-resonance probe and hardware, and the experiments proved that by replacing certain proline residues in bradykinin by α-methyl proline stabilized a beta-turn [24] conformation of the peptide. To support biosynthetic studies of John Robinson also deuterium and tritium NMR was applied.…”

Conformational analysis of hexapseudopeptides mimicking reverse turn structures induced by a modified (S)-proline. A combined spectroscopic and molecular dynamics investigation. Part 4

“…(Scheme 2 here) 1 H and 13 C NMR spectra were recorded on a Gemini spectrometer at 300 MHz (in about 15 mM solutions) using CDCl 3 as solvent. Chemical shifts are reported in ppm relative to CDCl 3 while the coupling constants (J) are in Hz.…”

“…Proline residues frequently occur in reverse turns and this is presumably due to their unique restricted φ angle, which is entropically favourable for turn folding. [13][14][15] In a recent paper, we reported on the synthesis of pseudo-tetrapeptides containing two L-valine units and two modified α-amino acids derived from proline and aspartic acid. The conformational analysis carried out on these unnatural peptides, pointed out the role of proline derivatives in originating β-and γ-folded conformers, thus acting as a scaffold promoting compact conformations.…”