The objective was to identify peptides with dual antioxidant and angiotensin I converting enzyme (ACE) inhibitory activities released from lentil proteins by Savinase®. The influence of gastrointestinal digestion on peptide bioactivity was also assayed. Fragments from vicilin, convicilin and legumin were the most abundant peptides identified. Peptides LLSGTQNQPSFLSGF, NSLTLPILRYL, TLEPNSVFLPVLLH showed the highest antioxidant (0.013-1.432μmol Trolox eq./μmol peptide) and ACE inhibitory activities (IC50=44-120μM). Gastrointestinal digestion of peptides improved their dual activity (10-14μmol Trolox eq./μmol peptide; IC50=11-21μM). In general, C-terminal heptapeptide was crucial for their dual activity. ACE inhibition relies on the formation of hydrogen bonds between C-terminal residues of lentil peptides and residues of the ACE catalytic site. The present study helps clarifying the relationship between structure and dual antioxidant/antihypertensive activity of lentil peptides opening new opportunities to food industry such as the application of lentil protein hydrolysates as ingredients for development of functional foods.

The transient receptor potential melastatin subtype 8 (TRPM8) is a cold sensor in humans, activated by low temperatures (>10, <28 °C), but also a polymodal ion channel, stimulated by voltage, pressure, cooling compounds (menthol, icilin), and hyperosmolarity. An increased number of experimental results indicate the implication of TRPM8 channels in cold thermal transduction and pain detection, transmission, and maintenance in different tissues and organs. These channels also have a repercussion on different kinds of life-threatening tumors and other pathologies, which include urinary and respiratory tract dysfunctions, dry eye disease, and obesity. This compendium firstly covers newly described papers on the expression of TRPM8 channels and their correlation with pathological states. An overview on the structural knowledge, after cryo-electron microscopy success in solving different TRPM8 structures, as well as some insights obtained from mutagenesis studies, will follow. Most recently described families of TRPM8 modulators are also covered, along with a section of molecules that have reached clinical trials. To finalize, authors provide an outline of the potential prospects in the TRPM8 field.

In view of the crucial role of protein-protein intercommunication both in biological and pathological processes, the search of modulators of protein-protein interactions (PPIs) is currently a challenging issue. The development of rational strategies to imitate key secondary structure elements of protein interfaces is complementary to other approaches based on the screening of synthetic or virtual libraries. In this sense, the present review provides representative examples of compounds that are able to disturb PPIs of therapeutic relevance, through the stabilization or the imitation of peptide hot-spots detected in contact areas of the interacting proteins. The review is divided into three sections, covering mimetics of the three main secondary structural elements found in proteins, in general, and in protein-protein interfaces, in particular (α-helices, β-sheets, and reverse turns). Once the secondary element has been identified, the first approach typically involves the translation of the primary peptide structure into different cyclic analogues. This is normally followed by gradual decrease of the peptide nature through combination of peptide and non-peptide fragments in the same molecule. The final step usually consists in the development of pertinent organic scaffolds for appending key functional groups in the right spatial disposition, as a means towards totally non-peptide small molecule PPI modulators.

Sequence determination of a region downstream from the vanXY_C gene in Enterococcus gallinarum BM4174 revealed an open reading frame, designated vanT, that encodes a 698‐amino‐acid polypeptide with an amino‐terminal domain containing 10 predicted transmembrane segments. The protein contained a highly conserved pyridoxal phosphate attachment site in the C‐terminal domain, typical of alanine racemases. The protein was overexpressed in Escherichia coli, and serine racemase activity was detected in the membrane but not in the cytoplasmic fraction after centrifugation of sonicated cells, whereas alanine racemase activity was located almost exclusively in the cytoplasm. When the protein was overexpressed as a polypeptide lacking the predicted transmembrane domain, serine racemase activity was detected in the cytoplasm. The serine racemase activity was partially (64%) inhibited by d‐cycloserine, whereas host alanine racemase activity was almost totally inhibited (97%). Serine racemase activity was also detected in membrane preparations of constitutively vancomycin‐resistant E. gallinarum BM4174 but not in BM4175, in which insertional inactivation of the vanC‐1d‐Ala:d‐Ser ligase gene probably had a polar effect on expression of the vanXY_C and vanT genes. Comparative modelling of the deduced C‐terminal domain was based on the alignment of VanT with the Alr alanine racemase from Bacillus stearothermophilus. The model revealed that almost all critical amino acids in the active site of Alr were conserved in VanT, indicating that the C‐terminal domain of VanT is likely to adopt a three‐dimensional structure similar to that of Alr and that the protein could exist as a dimer. These results indicate that the source of d‐serine for peptidoglycan synthesis in vancomycin‐resistant enterococci expressing the VanC phenotype involves racemization of l‐ to d‐serine by a membrane‐bound serine racemase.