Homo-oligomers constructed by using trans-2-aminocyclohexanecarboxylic acid monomers without protecting groups were studied. Both ab initio theory and NMR measurements showed that the tetramer tends to adopt a 10-helix motif, while the pentamer and hexamer form the known 14-helix. It was concluded that the conformationally constrained backbone is flexible enough to afford both 10-helical and 14-helical motifs, this observation in turn providing evidence of the true folding process. Self-association of the helical units was also detected, and the results of variable-temperature diffusion NMR measurements strongly suggested the presence of helical bundles in methanol solution.

In control: The secondary structure dependent self‐assembly of β‐peptides in solution proves that natural biopolymers are not unique in their highly structured conformational behavior. Stereochemically controlled secondary structural units of β‐peptide strands and helices intrinsically self‐associate into pleated‐sheet sandwiches (see picture) and helix‐bundle membranes, respectively.

Tris(8-quinolinolato)gallium(III) (KP46) and tris(maltolato)gallium(III) (GaM) are promising orally active antitumor metallodrugs currently undergoing clinical trials. Their interaction with human serum albumin (HSA) and transferrin (Tf) was studied in detail in aqueous solution by the combination of various methods such as spectrofluorometry, UV-vis spectrophotometry, (1)H and saturation transfer difference NMR spectroscopy, and ultrafiltration-UV-vis spectrophotometry. Binding data were evaluated quantitatively. Tf was found to replace the original ligand much less efficiently in KP46 than in GaM, whereas a significant noncovalent binding of KP46 with HSA (log K' = 4.04) retaining the coordination environment around gallium(III) was found. The interaction between HSA and KP46 was also confirmed by protein-complex modeling calculations. On the basis of the conditional stability constants, the distribution of gallium(III) in serum was computed and compared for these metallodrugs under physiological conditions, and revealed the prominent role of HSA in the case of KP46 and that of Tf for GaM.

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By means of simple or domino ring-closure reactions of 1-(α-aminobenzyl)-2-naphthol (Betti base: 1), 1-aminomethyl-2-naphthol (2) and 2-(α-aminobenzyl)-1-naphthol (reverse Betti base: 3) with phosgene, ethyl benzimidate, 2-carboxybenzaldehyde, levulinic acid, salicylaldehyde/formalin or salicylaldehyde/acetaldehyde, naphth[1,2-e][1,3]oxazine and naphth[2,1-e][1,3]oxazine derivatives were prepared. All of the nitrogen-bridged polycyclic derivatives of 1 and 3 containing a number of centers of asymmetry were formed with nearly complete diastereoselectivity. Considerable differences were observed in the ringclosing abilities of the unsubstituted and phenyl-substituted aminonaphthols 1 and 2 and of the regioisomeric compounds 1 and 3.

A series of novel curcuminoids were synthesised for the first time via a Mannich-3CR/organocatalysed Claisen-Schmidt condensation sequence. Structure-activity relationship (SAR) studies were performed by applying viability assays and holographic microscopic imaging to these curcumin analogues for anti-proliferative activity against A549 and H1975 lung adenocarcinoma cells. The TNFα-induced NF-κB inhibition and autophagy induction effects correlated strongly with the cytotoxic potential of the analogues. Significant inhibition of tumour growth was observed when the most potent analogue 44 was added in liposomes at one-sixth of the maximally tolerated dose in the A549 xenograft model. The novel spectrum of activity of these Mannich curcuminoids warrants further preclinical investigations.

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