The antioxidant peptide salamandrin-i: First bioactive peptide identified from skin secretion of salamandra genus (salamandra salamandra)

Amphibian skin is a multifunctional organ that plays key roles in defense, breathing, and water balance. In this study, skin secretion samples of the fire salamander (Salamandra salamandra) were separated using RP-HPLC and de novo sequenced using MALDI-TOF MS/MS. Next, we used an in silico platform to screen antioxidant molecules in the framework of density functional theory. One of the identified peptides, salamandrin-I, [M + H]+ = 1406.6 Da, was selected for solid-phase synthesis; it showed free radical scavenging activity against DPPH and ABTS radicals. Salamandrin-I did not show antimicrobial activity against Gram-positive and-negative bacteria. In vitro assays using human microglia and red blood cells showed that salamandrin-I has no cytotoxicity up to the concentration of 100 µM. In addition, in vivo toxicity tests on Galleria mellonella larvae resulted in no mortality at 20 and 40 mg/kg. Antioxidant peptides derived from natural sources are increasingly attracting interest. Among several applications, these peptides, such as salamandrin-I, can be used as templates in the design of novel antioxidant molecules that may contribute to devising strategies for more effective control of neurological disease.This work is financed by national funds through the FCT—Fundação para a Ciência e a Tecnologia, I.P., within the project No. PTDC/BII_BIO/31158/2017. A. Plácido is a recipient of a post-doctoral grant from the same project. A. Batagin-Neto and F.C.D.A. Lima thank the Brazilian National Council for Scientific and Technological Development (CNPq) (grants 420449/2018-3 and 428211/2018-6) for the financial support. This research was also supported by resources supplied by the Center for Scientific Computing (NCC/GridUNESP) of São Paulo State University (UNESP), CENAPAD/SP, and SICC-PRP/IFSP. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001