Synthesis of some 2,2′:6′,2"-terpyridines disubstituted in positions 6 and 6" with head-to-tail oriented amino acids and dipeptides:: A simple entry to a reversible inducer of folding in amino acid sequences

The 2,2':6',2 ''-terpyridine scaffold has been identified as a conformationally discrete structural element potentially capable of inducing reversible folding in substituents, attached through suitable spacers to its 6,6 ''-positions, by metal complexation/decomplexation or by protonadtion/deprotonation. The synthesis of some terpyridine-amino acids and terpyridine-dipeptide conjugates is described. The assembly of these conjugates has been achieved by connecting NH2- and CO2H-protected glycine, alanine, and valine residues or antiparallel oriented AlaGly/GlyAla chains to the terpyridine scaffold through phenylacetylene spacers. Preliminary experiments showed that upon addition of Zn2+, to the amino acid substituted transoid terpyridine systems, folded cisoid complexes were formed. Also, bis(protonation) of the dipeptide-substituted system resulted in the formation of a folded adduct. Reversibility of the folding process was shown by Zn2+ removal with triethylamine or deprotonation with aqueous ammonia. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).