Thomas Ruckle

Crystal structure of a synthetic cyclodecapeptide for template-assembled synthetic protein design

The structural prototype of a new generation of regioselectively addressable functionalized templates (RAFTs) for use in protein de novo design has been synthesized and crystallized. The structure of the aromatically substituted cyclodecapeptide was determined by X‐ray diffraction; it consists of an antiparallel β sheet spanned by heterochirally induced type II′ β turns, similar to that observed in gramicidin S. The three‐dimensional structure of the artificial template was also examined by an NMR spectroscopic analysis in solution and shown to be compatible with a β‐sheet plane suitable for accommodating secondary functional peptide fragments for the synthesis of template‐assembled synthetic proteins (TASPs).

Synthetic routes to NEtXaa4-cyclosporin A derivatives as potential anti-HIV I drugs

An efficient synthesis in 10 steps and overall yields up to 27% of NEtXaa(4)-cyclosporin A derivatives (Xaa = Leu, Val, Ile, Thr) starting from cyclosporin A is described. Biological activities of the new analogues show promising results for the design of cyclosporin derivatives exhibiting non-immunosuppressive and anti-HIV activity

Efficient one-pot synthesis of N-ethyl amino acids

Mono‐N‐ethylated α‐amino acid esters are obtained in high yields using reductive amination procedures. Formation of imine is achieved by excess of acetaldehyde, followed by removal of acetaldehyde and reduction by NaBH(OAc)3. The elaborated one‐pot synthesis allows for the efficient synthesis of side‐chain protected amino acid derivatives. Copyright

New Synthetic Routes to NEtXaa4-Cyclosporin Derivatives as Potential Anti-HIV Drugs

Since the discovery of the immunosuppresive activity of Cyclosporin A (CsA), considerable work has been devoted to the chemical synthesis of analogues. More recently, the finding of potential anti-HIV I activity of CsA evoked interest for the design of more selective cyclosporins active against HIV I but devoid of immunosuppresive activity. Based on previous observations that a N-methyl group at residue 4 is involved in one of the main metabolic degradation pathways [1], the synthesis of CsA analogues disposing various N-ethyl substituted residues at position 4 appeared particularly appealing for developing potential anti-HIV drugs [2]. Here we present the synthesis of new NEtXaa4CsA derivatives and their biological activities.