Exploiting Locusta migratoria as a source of bioactive peptides with anti-fibrosis properties using an in silico approach.

Edible insects have been proposed as an environmentally and economically sustainable source of protein, and are considered as an alternative food, especially to meat. The migratory locust, Locusta migratoria, is an edible species authorised by the European Union as a novel food. In addition to their nutritional value, edible insects are also sources of bioactive compounds. This study used an in silico approach to simulate the gastrointestinal digestion of selected L. migratoria proteins and posteriorly identify peptides capable of selectively inhibiting the N-subunit of the somatic angiotensin-I converting enzyme (sACE). The application of the molecular docking protocol enabled the identification of three peptides, namely TCDSL, IDCSR and EAEEGQF, which were predicted to act as potential selective inhibitors of the sACE N-domain and, therefore, possess bioactivity against cardiac and pulmonary fibrosis.

An in silico approach to unveil peptides from Acheta domesticus with potential bioactivity against hypertension, diabetes, cardiac and pulmonary fibrosis.

Entomophagy is a sustainable alternative source of proteins for human nutrition. Acheta domesticus is one of the three insect species that complies with the European Union Regulation on novel foods, but to date, there are no reports on their potential bioactive peptides. In this study, an in silico approach was applied to simulate the gastrointestinal (GI) digestion of six A. domesticus proteins and identify new peptides with potential anti-hypertensive and/or anti-diabetic properties, resulting from their capability to inhibit the somatic Angiotensin-I converting enzyme (sACE) and/or dipeptidyl peptidase 4 (DPP-4), respectively. A molecular docking protocol was applied to evaluate the binding interactions between the 43 peptides ranked with high probability of being bioactive and three drug targets: DPP-4 and two catalytic domains (N- and C-) of sACE. Five peptides (AVQPCF, CAIAW, IIIGW, DATW and QIVW) showed high docking scores for both enzymes, suggesting their potential to inhibit the DPP-4 and both catalytic domains of sACE, thus possessing multifunctional bioactive properties. Two peptides (PIVCF and DVW) showed higher docking scores for the N-domain of sACE, indicating a potential action as selective inhibitors and consequently with anti-cardiac and pulmonary fibrosis bioactivities. This is the first study identifying peptides originated from the simulated GI digestion of A. domesticus with potential activities against hypertension, diabetes, cardiac and pulmonary fibrosis.

Current Status of the Use of Multifunctional Enzymes as Anti-Cancer Drug Targets.

Fighting cancer is one of the major challenges of the 21st century. Among recently proposed treatments, molecular-targeted therapies are attracting particular attention. The potential targets of such therapies include a group of enzymes that possess the capability to catalyze at least two different reactions, so-called multifunctional enzymes. The features of such enzymes can be used to good advantage in the development of potent selective inhibitors. This review discusses the potential of multifunctional enzymes as anti-cancer drug targets along with the current status of research into four enzymes which by their inhibition have already demonstrated promising anti-cancer effects in vivo, in vitro, or both. These are PFK-2/FBPase-2 (involved in glucose homeostasis), ATIC (involved in purine biosynthesis), LTA4H (involved in the inflammation process) and Jmjd6 (involved in histone and non-histone posttranslational modifications). Currently, only LTA4H and PFK-2/FBPase-2 have inhibitors in active clinical development. However, there are several studies proposing potential inhibitors targeting these four enzymes that, when used alone or in association with other drugs, may provide new alternatives for preventing cancer cell growth and proliferation and increasing the life expectancy of patients.

A Molecular Perspective on Sirtuin Activity.

The protein acetylation of either the α-amino groups of amino-terminal residues or of internal lysine or cysteine residues is one of the major posttranslational protein modifications that occur in the cell with repercussions at the protein as well as at the metabolome level. The lysine acetylation status is determined by the opposing activities of lysine acetyltransferases (KATs) and lysine deacetylases (KDACs), which add and remove acetyl groups from proteins, respectively. A special group of KDACs, named sirtuins, that require NAD+ as a substrate have received particular attention in recent years. They play critical roles in metabolism, and their abnormal activity has been implicated in several diseases. Conversely, the modulation of their activity has been associated with protection from age-related cardiovascular and metabolic diseases and with increased longevity. The benefits of either activating or inhibiting these enzymes have turned sirtuins into attractive therapeutic targets, and considerable effort has been directed toward developing specific sirtuin modulators. This review summarizes the protein acylation/deacylation processes with a special focus on the current developments in the sirtuin research field.