Crystal structure of Boc‐LAla‐ΔPhe‐ΔPhe‐ΔPhe‐ΔPhe‐NHMe: a left‐handed helical peptide

Abstract

αβ‐Dehydrophenylalanine residues constrain the peptide backbone to β‐bend conformation. A pentapeptide containing four consecutive (APhe) residues has been synthesised and crystallised. The peptide Boc‐LAla‐ΔPhe‐ΔPhe‐ΔPhe‐ΔPhe‐NHMe (C45H46N6O7, MW = 782.86) was crystallised from an acetonitrile/ methanol mixture. The crystal belongs to the orthorhombic space group P212121 with a = 19.455(6), b = 20.912(9), c = 11.455(4) Å and Z = 4. The X‐ray (MoKα, lD = 0.7107 Å) intensity data were collected using the Rigaku‐AFC7 diffractrometer. The crystal structure was determined by direct methods and refined using the least‐squares technique, R = 8.41% for 1827 reflections with ‖F0‖ > 4σ‖Fo‖. The molecule contains the largest stretch of consecutive dehydrophenylalanine residues whose crystal structure has been determined so far. The peptide adopts left‐handed 310‐helical conformation despite the presence of LAla at the N‐terminus. The mean ø, Ψ values, averaged across the last four residues are 56.8° and 17.5°, respectively. There are four 41 intramolecular hydrogen bonds, characteristic of the 310‐helix. In the crystal each molecule interacts with four crystallographically symmetric molecules with one hydrogen bond each.

Transfer of Noncovalent Chiral Information along an Optically Inactive Helical Peptide Chain: Allosteric Control of Asymmetry of the C-Terminal Site by External Molecule that Binds to the N-Terminal Site

“…Control of helical sense has been extensively investigated using artificial helical models based on achiral monomer units. ,− Here the helical sense of such an optically inactive segment is induced by covalent or noncovalent chiral stimuli. ,− These leading studies provide significant guidance as to how chiral information transfers along a molecular chain to generate a one-handed helix. Such an optically inactive helix usually involves chromophoric groups in the main chain or side chain.…”

Handedness preference and switching of peptide helices. Part II: Helices based on noncodedα‐amino acids

“…Induced CD proved to be an excellent tool to determine the solution conformation of peptides based on the achiral ΔPhe residue, especially in detecting the screw sense of the helices formed. It is principally for this reason that the number of publications on this topic is huge . The Δ Z Phe‐containing peptides show different CD curves in the near‐UV region depending on the main‐chain length and on the position in the sequence and number of the Δ Z Phe residues.…”

“…As in the case of the aforementioned Aib peptides discussed, many ΔPhe‐containing linear peptides are highly crystalline materials. This property allows X‐ray diffraction analyses to be performed . Almost all of them are characterized by the Δ Z Phe configurational isomer.…”

Influence of solvents on conformation of dehydropeptides

“…Previous studies indicate, that the influence of D-amino acid residue on peptide conformation depends on several factors. The most crucial is number of D-amino acid residues introduced into the peptide chain [4][5][6][7] as well as size of substituent on the C b atom of both: dehydroamino acid residue [8][9][10][11] and neighboring amino acid residue [6,[12][13][14][15][16][17][18][19][20]. Apart from these factors listed before, specific for the dehydropeptide, also other parameters, specific for the environment, have a strong influence on spatial conformation of the peptide chain.…”