A bound conformation of the antigenic decapeptide hen egg lysozyme HEL[52-61] associated to the mouse MHC class II (MHC II) I-Ak was modeled by homology with the three-dimensional structure of hemagglutinin HA[306-318]-HLA-DR1 complex. HEL peptide Tyr53 could not be aligned with the HA peptide Tyr308 because this resulted in a buried Tyr53 side chain within the I-Ak peptide-binding groove and this conflicted with this side chain being recognized by T cells. Therefore, Asp52 of HEL was fixed as the P1 anchor and aligned on Tyr308 of HA. After molecular dynamics, the modeled complex was stable even in the absence of any constraint. The peptide backbone adopted a polyproline II-like conformation with canonical hydrogen bonding between the peptide backbone and MHC II molecule. Asp52, IIe55, Gin57 and Ser60 were predicted to be deeply buried into P1, P4, P6 and P9 MHC II pockets, and Tyr53, Leu56, Asn59 and Arg61 as TCR contacting residues. The modeling of 15 complexes associating I-Ak with peptides derived from HEL[52-61] by single amino acid substitution proved stable with conserved hydrogen bonds and side chain orientation compatible with their recognition by two T cell hybridomas. Moreover, comparison with the recently solved crystal structure of the related HEL[50-62]-I-Ak complex revealed striking similarities.

The objective of this study was to unravel the changes in property space resulting from the amino‐acid‐to‐residue transformation. Conformation‐dependent lipophilicity was chosen as the metric to assess changes in property spaces. Phe, Ala‐Phe‐Ala, Gln, and Ala‐Gln‐Ala were first submitted to a conformational search strategy using quenched molecular dynamics in order to obtain an efficient sampling of a conformational space. This search was performed for the four electrical forms of the compounds (cationic, zwitterionic, uncharged, and anionic). The virtual lipophilicity (logP) of each conformer was then calculated by the Molecular Lipophilicity Potential (MLP). Similarly, the lipophilicity increment of the Phe and Gln residues in all electrical states and conformers of Ala‐Phe‐Ala and Ala‐Gln‐Ala, respectively, were calculated by the MLP. As expected, the results showed a marked expansion in the property space of a tripeptide compared to an amino acid. However, they also revealed a marked reduction in property space resulting from the amino‐acid‐to‐residue transformation.

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The analogue of zeatin bearing a vinylic fluorine atom and its geometrical isomer were synthesized. The fluorine atom exerts a favorable influence on cytokinin activity in the fluoro analogue of cis-zeatin, but not in the fluoro analogue of zeatin itself. Another series of zeatin derivatives in which the methyl group was replaced by alkyl (ethyl, propyl, and isopropyl), phenyl, and benzyl groups were also obtained. The ethyl analogue was found to be more active than zeatin, while the others were inactive or slightly active. Keywords: Cytokinins; fluoro compounds; synthesis; biological activity