What is it about?
Therapeutic peptides have demonstrated high clinical applicability. Nevertheless, their physicochemical properties hamper the direct administration of a peptide into the human body in most cases. Numerous groups have developed strategies to address this issue. One of the most interesting approaches is the engineering of peptide-Fc fusion proteins. This fusion proteins, elegantly known as Peptibodies, are chimeric proteins generated by fusing a bioactive peptide with the Fc domain of IgG, resembling an antibody.
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Why is it important?
Free peptides have little or no resistance to cleavage by serum/tissue proteases. Their conjugation to an Fc domain of IgG, generating a peptibody, avoids the proteases recognition and takes advantage of the protective role of the FcRn recycling pathway. The mechanism of action of peptibodies also mimic the therapeutic antibodies. They can act directly on cell membranes, which can kill the cells, or can interact with membrane/soluble receptors activating/disabling cellular pathways. The inclusion of a minimum of two peptides per peptibody also increases their activity and avidity. These better properties over free peptides increased the therapeutic applications of peptibodies.
Perspectives
Our review covers the issue of Peptibodies and their translation into the clinic. Their mechanism of action and pharmacokinetic properties; challenges associated with their manufacturing; and examples of peptibodies currently on the market are addressed. In addition, a reflexion on the challenges associated with therapeutic peptides and the strategies used by researchers to circumvent them are also addressed. In the end we highlight the main problems associated with the Peptibodies.
Vera Neves
Read the Original
This page is a summary of: Peptibodies: An elegant solution for a long-standing problem, Peptide Science, January 2018, Wiley,
DOI: 10.1002/bip.23095.
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