Structural determinants conferring unusual long life in human serum to rattlesnake‐derived antimicrobial peptide Ctn(15‐34)

Pérez‐Peinado, Clara; Dias, Susana; Mendonça, Diogo A.; Castanho, Miguel A. R. B.; Veiga, Ana Salomé; Andreu, David

http://hdl.handle.net/10451/49982

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Autores

Pérez‐Peinado, Clara

Dias, Susana

Mendonça, Diogo A.

Castanho, Miguel A. R. B.

Veiga, Ana Salomé

Andreu, David

Resumo(s)

Ctn[15-34], a downsized version of the snake venom cathelicidin-like peptide crotalicidin (Ctn), shows an unusually high lifespan (t1/2 , approximately 12 h) in human serum, which significantly adds to its promise as an antimicrobial and antitumor agent. Herein we investigate the role of Ctn[15-34] structure on serum survival. Using a set of analogs, we show that C-terminal amidation, as well as the specific layout of the Ctn[15-34] sequence-a helical N-terminal domain followed by a hydrophobic domain-is crucial for slow degradation, and any change in their arrangement results in significantly lower t1/2 . Aside from the privileged primary structure, features such as self-aggregation can be ruled out as causes for the long serum life. Instead, studies in other protease-rich fluids suggest a key role for certain human serum components. Finally, we demonstrate that Ctn[15-34] is able to induce bacterial death even after 12-hour pre-incubation in serum, in agreement with the proteolytic data. Altogether, the results shed light on the uncommon stability of Ctn[15-34] in human serum and confirm its potential as an anti-infective lead.