Synthetic peptides mimicking the interleukin-6/gp130 interaction: A two-helix bundle system. Design and conformational studies

The objective of our study was to mimic in a typical reductionist approach the mol. interactions obsd. at the interface between the gp130 receptor and interleukin-6 during formation of their complex. A peptide system obtained by reproducing some of the interleukin-6/gp130 mol. interactions into a two-helix bundle structure was investigated. The soln. conformational features of this system were detd. by CD and NMR techniques. The CD titrn. expts. demonstrated that the interaction between the designed peptides is specific and based on a well-defined stoichiometry. The NMR data confirmed some of the structural features of the binding mechanism as predicted by the rational design and indicated that under our conditions the recognition specificity and affinity can be explained by the formation of a two-helix bundle. Thus, the data reported herein represent a promising indication on how to develop new peptides able to interfere with formation of the interleukin-6/gp130 complex.