A synthetic peptide reproducing the mitochondrial targeting motif of AKAP121: A conformational study

The conformational features of a peptide derived by the 10-30 sequence of the mitochondrial domain of AKAP121 [Ac-1XKKPLALPGMLALLGWWWFFSRKKX25-NH2 (X = (beta)-Ala)] in water and in a water/triflouroethanol (TFE) mixture at 298 K have been determined by NMR and CD spectroscopy. Backbone clustering analysis of NMRderived structures led to the identification of a single representative structure in water/TFE. The structure of the peptide consists mainly of an (alpha)-helix, whose core is the region 7-23, with a less ordered N-terminal part. These data are confirmed by CD analysis. It is noteworthy that the high hydrophobic Trp16-Phe20 segment, that might also mediate interaction with tubulin, is organized in an (alpha)-helical wheel. Our conformational data can be the starting point for the development of highly selective peptides that interfere with the biological function of the Protein Kinase A scaffold protein AKAP121.