Odorranain-P-RA2 peptide precursor

Xenin, a 25 amino acid peptide, has been identified in human gastric mucosa in the search for a counterpart to the amphibian octapeptide xenopsin. Xenin is structurally related also to the hypothalamic and ileal peptide neurotensin and is, therefore, a member of the xenopsin/neurotensin/xenin peptide family. The biological activities of these peptides are similar: Xenin has been shown to inhibit pentagastrin-stimulated secretion of acid, to induce exocrine pancreatic secretion and to affect small and large intestinal motility. In the gut, xenin interacts with the neurotensin receptor. Radioimmunoassay and chromatography of postprandial plasma in humans indicate the release of xenin into the circulation. The identification of a 35-amino acid precursor peptide of xenin - proxenin, and a review of the Gen-bank revealed that xenin represents the N terminus of a cytosolic coat protein (alpha-COP) from which xenin can be cleaved by aspartic proteinases such as pepsin and cathepsin E. The physiological role of the peptide xenin is not known.

BACE1 (β-secretase, memapsin 2, Asp2) has emerged as a promising target for the treatment of Alzheimer's disease. BACE1 is an aspartic protease which functions in the first step of the pathway leading to the production and deposition of amyloid-β peptide (Aβ). Its gene deletion showed only mild phenotypes. BACE1 inhibition has direct implications in the Alzheimer's disease pathology without largely affecting viability. However, inhibiting BACE1 selectively in vivo has presented many challenges to medicinal chemists. Since its identification in 2000, inhibitors covering many different structural classes have been designed and developed. These inhibitors can be largely classified as either peptidomimetic or non-peptidic inhibitors. Progress in these fields resulted in inhibitors that contain many targeted drug-like characteristics. In this review, we describe structure-based design strategies and evolution of a wide range of BACE1 inhibitors including compounds that have been shown to reduce brain Aβ, rescue the cognitive decline in transgenic AD mice and inhibitor drug candidates that are currently in clinical trials.

Thousands of naturally occurring peptides differing in their origin, abundance and possible functions have been identified in the tissue and biological fluids of vertebrates, insects, fungi, plants and bacteria. These peptide pools are referred to as intracellular or extracellular peptidomes, and besides a small proportion of well-characterized peptide hormones and defense peptides, are poorly characterized. However, a growing body of evidence suggests that unknown bioactive peptides are hidden in the peptidomes of different organisms. In this review, we present a comprehensive overview of the mechanisms of generation and properties of peptidomes across different organisms. Based on their origin, we propose three large peptide groups-functional protein "degradome", small open reading frame (smORF)-encoded peptides (smORFome) and specific precursor-derived peptides. The composition of peptide pools identified by mass-spectrometry analysis in human cells, plants, yeast and bacteria is compared and discussed. The functions of different peptide groups, for example the role of the "degradome" in promoting defense signaling, are also considered.