Studies on the chemical synthesis of the Id proteins and mutated analogs

ORGN 560

Chiara Cabrele, chiara.cabrele@chemie.uni-regensburg.de, Sebastian Kiewitz, Jaroslava Havrdová, and Noemi Colombo. Department of Chemistry, Universität Regensburg, Universitätsstr. 31, Regensburg, 93053, Germany
Id proteins are members of the family of the helix-loop-helix (HLH) transcription factors and function as dominant negative regulators of the DNA transcription. We have investigated the accessibility to these four proteins, Id1-4, by stepwise solid-phase synthesis and Fmoc-chemistry. The success of the syntheses was found to strongly depend on the protein. Unlike the high sequence identity of the HLH-Id motifs, the primary structure of the C-terminal regions is unique for each Id protein and presented a chain-assembly difficulty that varied from low for Id3 to very high for Id2. In the latter case the poor homogeneity of the final products has been attributed to a difficult Ile/Leu-rich fragment spanning 19 residues within the Id2-C-terminus, which is not present in the other Id proteins. Here we present the results toward the Id-protein total synthesis and conformational analysis.