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 molecular interactions observed 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 molecular interactions into a two-helix bundle structure was investigated. The solution conformational features of this system were determined by CD and NMR techniques. The CD titration experiments 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.
Zaccaro
Laura
L
Istituto di Biostrutture e Bioimmagini, C.N.R., Dipartimento di Chimica Biologica, Università Federico II di Napoli, 80134 Napoli, Italy.
Bucci
Enrico
E
Vitale
Rosa Maria
RM
Perretta
Giuseppe
G
Fattorusso
Roberto
R
Benedetti
Ettore
E
Saviano
Michele
M
Pedone
Carlo
C
D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D050822:Cytokine Receptor gp130; D015850:Interleukin-6 / Q000737:chemistry* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D015703:Antigens, CD; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D010455:Peptides; D050822:Cytokine Receptor gp130