Elke Otto Livres

A delightfully illustrated introduction to gardening and nature for the younger reader, full of ideas and informative descriptions of the animals and plants found in the garden.

This thesis presents the rational design and synthesis of head-to-tail-cyclized peptide libraries featuring the novel binding motif isoDGR. It explores the reasons behind the observed differences in selectivity and activity of the developed libraries. The initial approach emulated the sequence of the highly active cyclo(-RGDfV-), while the second mirrored the Gly-flanked NGR loop. However, the resulting peptides exhibited only moderate activity or were entirely inactive. The retro-inverso approach also resulted in inactivity. Notably, the introduction of various aromatic residues (X) adjacent to isoAsp in the cyclic pentapeptides cyclo(-X-isoDGR-G-) led to the identification of a potent candidate: compound 27, cyclo(-phg-isoDGR-G-), which is a highly active and selective α5β1 ligand. Conversely, placing the aromatic residue next to Arg enhanced affinity for αvβ3, particularly with compound 76, cyclo(-G-isoDGR-phg-). The head-to-tail-cyclized isoDGR peptides lack free α-amino groups, allowing for direct comparisons of stereochemistry and flanking residue influence. The constrained cyclic peptides affect selectivity for αvβ3 or α5β1 integrins based on aromatic substitutions. Additionally, the orientation of key residues and their stereochemical control related to activity were examined. The binding capacity and specificity of compounds 27 and 76 in living cells aligned well with in vitro findings, highlighting their potential in

Wasserarbeit, Wasserrettung, Seenotrettung: Für alle Hunderassen mit praktischen Tipps und allen Prüfungsfragen