Rational development of novel leads from animal secretion based on coagulation and cell targets: 1. In silico analysis to explore a peptide derivative as lipocalins' signature

Abstract

Animal venoms and secretions have been screened, in our research group, to discover, identify and isolate peptide molecules active in the mammalian haemostatic system. As result, this kind of research has provided a portfolio of promising drug candidates. These novel recombinant proteins have turned out to be multifunctional molecules, and are currently under different development phases. Lopap from bristles of the Lonomia obliqua moth caterpillar, for instance, is a prothrombin activator which belongs to the lipocalin family. It displays serine protease-like activity with procoagulant effect, and also induces cytokine secretion and antiapoptotic pathways in human cultured endothelial cells. Furthermore, a Lopap-derived peptide has showed to induce collagen synthesis in fibroblast culture and in animal dermis. Here, the molecular properties (steric, electronic, hydrophobic, geometric), which are strongly dependent on chemical structure, were investigated by applying chemometric and computational chemistry methods. It was considered different patterns of amino acid substitution related to the lipocalins' motif 2, which was recently shown to modulate cell survival. The calculated molecular properties were generally maintained in all investigated peptides extracted from three-dimensional structures of Protein Data Bank (1t0v, 1bbp, 1kxo, 2hzr, 1iiu, 1jyj, 1gka, 1s44, 3ebw) when compared to Lopap-derived peptide, specially the molecular shape and electronic density distribution, validating the lipocalin sequence signature previously reported. Indeed, those two properties are quite important for the molecular recognition process.