Structural properties of cyclic peptides containing cis- or trans-2-aminocyclohexane carboxylic acid

Strijowski U, Sewald N. Structural properties of cyclic peptides containing cis- or trans-2-aminocyclohexane carboxylic acid. ORGANIC & BIOMOLECULAR CHEMISTRY. 2004;2(8):1105-1109.A series of cyclic peptides containing either cis- or trans-2-aminocyclohexane carboxylic acid as mimics for L-proline has been synthesized and their structural properties have been investigated using NMR and MD methods

An improved method for the solution cyclization of peptides under pseudo-high dilution conditions

Malesevic M, Strijowski U, Bachle D, Sewald N. An improved method for the solution cyclization of peptides under pseudo-high dilution conditions. Journal of Biotechnology. 2004;112(1-2):73-77.Depending on the ring size, the cyclization of peptides often is accompanied by dimerization or cyclodimerization. Hence, these macrocyclizations have to be performed under high dilution conditions. Efficient cyclization of peptides in solution with a minimum amount of solvent succeeds, when a dual syringe pump is used to simultaneously add the linear peptide precursor and a coupling reagent from two separate syringes. (C) 2004 Elsevier B.V. All rights reserved

Spectroscopic detection of pseudo-turns in homodetic cyclic penta- and hexapeptides comprising beta-homoproline

Malesevic M, Majer Z, Vass E, et al. Spectroscopic detection of pseudo-turns in homodetic cyclic penta- and hexapeptides comprising beta-homoproline. INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS. 2006;12(2):165-177.beta-Amino acids with side chains at C-2 and/or at C-3 are of growing interest in drug design, as they may induce astonishing and unusual peptide conformations. Therefore it is of eminent importance to gather information on the consequences of beta-amino acid incorporation on the three-dimensional structure of a peptide. This paper describes the synthesis and conformational analysis of cyclic penta- and hexapeptides comprising either (S)-Pro or (S)-beta-Hpro. The conformational influence of the beta-homoproline building block was analyzed by the combined application of CD, FT-IR and NMR. While the CD spectra of the proline containing peptides indicate the presence of inverse gamma-turns and beta II-turns, the CD spectra of the beta-homoamino acid analogs are dominated by an unprecedented negative band near 205 nm associated with a pseudo-beta-turn (Psi beta) or pseudo-gamma-turn (Psi gamma). These results were confirmed by FT-IR spectroscopy, which also indicates the formation of two internal hydrogen bonds in the cyclic peptides containing the beta-homoproline. The conformations of the beta-homoproline containing pentapeptides were additionally determined by NMR in combination with MD simulations in two different solvents. The conformation in trifluoroethanol (TFE) is characterized by a bifurcated hydrogen bond stabilizing a pseudo-gamma-turn with beta-homoproline in the central position, nested with a pseudo-beta-turn with beta-homoproline in the i + l position. The combined CD/FT-IR studies clearly show that the replacement of proline by beta-homoproline gives rise to a more flexible peptide backbone, and CD spectroscopy hints towards the presence of pseudo-beta- or pseudo-gamma-turns