Chemometric analysis of Hymenoptera toxins and defensins: A model for predicting the biological activity of novel peptides from venoms and hemolymph

Abstract

When searching for prospective novel peptides, it is difficult to determine the biological activity of a peptide based only on its sequence. The "trial and error" approach is generally laborious, expensive and time consuming due to the large number of different experimental setups required to cover a reasonable number of biological assays. To simulate a virtual model for Hymenoptera insects, 166 peptides were selected from the venoms and hemolymphs of wasps, bees and ants and applied to a mathematical model of multivariate analysis, with nine different chemometric components: GRAVY, aliphaticity index, number of disulfide bonds, total residues, net charge, pI value, Boman index, percentage of alpha helix, and flexibility prediction. Principal component analysis (PCA) with non-linear iterative projections by alternating least-squares (NIPALS) algorithm was performed, without including any information about the biological activity of the peptides. This analysis permitted the grouping of peptides in a way that strongly correlated to the biological function of the peptides. Six different groupings were observed, which seemed to correspond to the following groups: chemotactic peptides, mastoparans, tachykinins, kinins, antibiotic peptides, and a group of long peptides with one or two disulfide bonds and with biological activities that are not yet clearly defined. The partial overlap between the mastoparans group and the chemotactic peptides, tachykinins, kinins and antibiotic peptides in the PCA score plot may be used to explain the frequent reports in the literature about the multifunctionality of some of these peptides. The mathematical model used in the present investigation can be used to predict the biological activities of novel peptides in this system, and it may also be easily applied to other biological systems.

Agelaia MP-I: A peptide isolated from the venom of the social wasp, Agelaia pallipes pallipes, enhances insulin secretion in mice pancreatic islets

“…3 shows the charge distribution along the sequence. These characteristics of a high percentage of alpha helices, net charge, and hydrophobicity are in accordance with the PCA grouping of this peptide, as described recently by Saidemberg et al (2011). The molecular modeling of this peptide is fundamental for understanding its activity in relation to structure.…”

“…AMP-I sequence differs from the original Mastoparan peptide (from Vespula lewisii), as shown in Table 1. However, considering the characteristics of the data obtained to develop the molecular modeling of AMP-I, the results of biological assays of hemolysis (ED 50 ¼ 6 Â 10 À6 M) and mast cell degranulation (ED 50 ¼ 4 Â 10 À5 M)obtained by Baptista- Saidemberg et al (2011), besides in silico classification using physicochemical properties by PCA it is possible to confirm that AMP-I is also a mastoparan class peptide.…”

“…Mastoparan and its analogue are also reported to interact with G proteins (Weingarten et al, 1990;Wakamatsu et al, 1992), therefore due to the similarity of AMP-I with Mastoparan-X, a very well described G protein interacting peptide (Sukumar and Higashijima, 1992;Wakamatsu et al, 1992), this is a very good clue about the mechanism of action of AMP-I, since several important sites regulating stimulus-secretion coupling and release of insulin from pancreatic beta-cells are modulated by G proteins (Robertson et al, 1991). The principal component analysis (PCA) classification, described by Saidemberg et al (2011), of the Mastoparans also indicates that some edge peptides from this large class, in addition to having similar general physico-chemical properties, can show some superposition with other peptide groups. Therefore, besides having the same general activities, different mastoparans can have different mechanisms of action and properties.…”

“…The studies were carried out on 90-days-old male Swiss mice obtained from the breeding colony at UNICAMP and maintained at 22 AE 1 C, on a 12-h light-dark cycle, with free access to food and water. Table 1 Amino acid sequences for Agelaia MP-I described by Mendes et al (2004) and revisited by Baptista- Saidemberg et al (2011), Mastoparan described by Hirai et al (1979a), and Mastoparan-X described by Hirai et al (1979b) aligned by multialign software (http://multalin.toulouse.inra.fr/multalin/ cgi-bin/multalin.pl, accessed in November 24th, 2011). The red color indicates that the amino acid residue is present in all peptides.…”

The effects of the C-terminal amidation of mastoparans on their biological actions and interactions with membrane-mimetic systems

“…Mastoparans are polycationic peptides from the venoms of social wasps, presenting amphipathic helical structures capable of inducing mast cell degranulation and/or the lysis of mast cell membranes, hemolysis and sometimes antimicrobial actions [36]. The degranulating activity appears to be related to the activation of G-protein coupled receptors in the mast cells, while the other activities mentioned above are ascribed to the ability of the peptides to interact with the cell membrane surface via the positively charged side-chains of their amphipathic α-helical structures [37].…”