A decapeptide Boc-L-Ala-(Delta Delta Phe)(4)-L-Ala-(Delta Delta Phe)3-Gly-OMe (Peptide I) was synthesized to study the preferred screw sense of consecutive alpha,beta-dehydrophenylalanine (Delta Delta Phe) residues. Crystallographic and CD studies suggest that, despite the presence of two L-Ala residues in the sequence, the decapeptide does not have a preferred screw sense. The peptide crystallizes with two conformers per asymmetric unit, one of them a slightly distorted right-handed 3(10)-helix (X) and the other a left-handed 3(10)-helix (Y) with X and Y being antiparallel to each other. An unanticipated and interesting observation is that in the solid state, the two shape-complement molecules self-assemble and interact with an extensive network of C-H...O hydrogen bonds and pi-pi interactions, directed laterally to the helix axis with amazing regularity. Here, we present an atomic resolution picture of the weak interaction mediated mutual recognition of two secondary structural elements and its possible implication in understanding the specific folding of the hydrophobic core of globular proteins and exploitation in future work on de novo design.

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The temperature-dependent secondary-structural changes in the two known helical model peptides Boc-Val-deltaPhe-Ala-Leu-Gly-OMe (1; alpha-helical) and Boc-Leu-Phe-Ala-deltaPhe-Leu-OMe (2; 3(10)-helical), which both comprise a single dehydrophenylalanine (deltaPhe) residue, were investigated by means of FT-IR spectroscopy (peptide film on KBr). Both the first-order and the better-resolved second-order derivative IR spectra of 1 and 2 were analyzed. The nu(NH) (3240-3340 cm(-1)), the Amide-I (1600-1700 cm(-1)), and the Amide-II (1510-1580 cm(-1)) regions of 1 and 2 showed significant differences in thermal-denaturation experiments (22 degrees --> 144 degrees), with the 3(10)-helical peptide (2) being considerably more stable. This observation was rationalized by different patterns and strengths of intramolecular H-bonds, and was qualitatively related to the different geometries of the peptides. Also, a fair degree of residual secondary-structural elements were found even in the 'denatured' states above 104 degrees (1) or 134 degrees (2).

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.

The mechanism underlying the autoimmune polyglandular syndrome type-1 (APS1) has been attributed to defective T-cell negative selection resulting from reduced expression and presentation of autoantigens in thymic medullary epithelial cells (MECs). It has also been postulated that Aire is involved in development of regulatory T cells, although supporting evidence is lacking. Here we show that expression of Aire in MECs is required for development of iNKT cells, suggesting a role for iNKT cells in APS1.