Design and Production of Chimeric Resilin-like Polypeptides (RLPs)

In this chapter, an overview of “engineered” chimeric polypeptides containing resilin sequences will be presented. Chimeric polypeptides contain sequences inspired by different proteins. They are appealing as biomaterials because their design relies on the aim to add physicochemical and biological functionalities to the polypeptide, obtaining tunable materials. Herein, emphasis will be devoted to the design strategy and the cloning strategy for the production of the recombinant polypeptides and their mechanical properties. Sequentially, the potential applications proposed for chimeric RLPs will be described. The last paragraph will be dedicated to future perspectives of chimeric polypeptides in the framework of biomimetic materials and biomaterials science, taking into account the principal advantages and the main critical drawbacks to be solved in the future. “A mingled monster, of no mortal kind; Behind, a dragon's fiery tail was spread; A goat's rough body bore a lion's head; Her pitchy nostrils flaky flames expire; Her gaping throat emits infernal fire….” Iliad, VI, (trad A. Pope

Tumor Necrosis Factor-a Neutralizing Antibodies Induced by a Glycolaldehyde-Modified C- terminal Polypeptide.

TNF-a is a pro-inflammatory cytokine that is overexpressed in diverse inflammatory states such as rheumatoid arthritis. Anti-TNF therapies, including monoclonal antibodies (Abs), have demonstrated remarkable success in management of arthritis and other chronic inflammatory diseases. The possibility to elicit autoAbs to TNF-a (beneficial autoimmunity) has been proposed as an immunotherapeutic approach to neutralize systemic TNF-a (1). Studies using a DNA vaccination strategy in rat adjuvant arthritis mapped several epitopes for natural anti-TNF-a autoAbs in the C-terminal portion of the sequence. We previously showed that aldehyde-tagged peptide conjugates representing immunogenic epitopes of toxic shock syndrome toxin–1, could induce anti-toxin neutralizing Abs without the need of potent adjuvants (2). In the present study, using a C-terminal TNF-a recombinant polypeptide, we followed a similar approach to generate neutralizing Abs against TNF-a in Lewis rats. Immunized rats showed less severe symptoms in the collagen induced arthritis ( CIA) model. 1. Dalum I. et. al. Therapeutic antibodies elicited by immunization against TNF-alpha. Nat Biotechnol 1999. 17:666-669. 2. Bavoso A, Ostuni A, De Vendel J, Pollaro F, Armentano F, Knight T, Makker S. and A. Tramontano. Aldehyde modification of peptide immunogen enhances protein-reactive antibody response to toxic shock syndrome toxin-1. J Pept Sci 2006. 12:843-849