Current Protein and Peptide Science - Volume 14, Issue 6, 2013

It is well established in the scientific literature that only a small fraction of microorganisms can be cultured by conventional microbiology methods. The ever cheaper and faster DNA sequencing methods, together with advances in bioinformatics, have improved our understanding of the structure and functional behavior of microbial communities in many complex environments. However, the metagenomics approach alone cannot elucidate the functionality of all microorganisms, because a vast number of potentially new genes have no homologs in public databases. Metatranscriptomics and metaproteomics are approaches based on different techniques and have recently emerged as promising techniques to describe microbial activities within a given environment at the molecular level. In this review, we will discuss current developments and applications of metagenomics, metatranscriptomics and metaproteomics, and their limitations in the study of microbial communities. The combined analysis of genes, mRNA and protein in complex microbial environments will be key to identify novel biological molecules for biotechnological purposes.

The Renin-Angiotensin-System (RAS) molecular network has been widely studied, especially with attention to angiotensin II, the main effector peptide among RAS. The relation of Ang II to hypertension pathogenesis has led to research being extended to other molecules from the RAS, such as angiotensin III and IV, angiotensin (1-5), and angiotensin (1-9). Moreover, great pharmacologic advances have been made in hypertension treatment by inhibiting renin and angiotensin converting enzymes and blocking the bonding of angiotensin II to its receptor AT1. Thus, RAS molecular signaling and its effect on blood pressure as well as its relationship to renal function and cardiovascular disease are still being investigated. It is a great challenge to fully cover and understand all molecules from the RAS, especially those that interfere with or have vasoactive properties. Some of these targets respond to exercise, stimulating nitric oxide synthesis and endothelial vasodilation. The activation of these specific molecules via exercise is a systematic way of controlling high blood pressure without pharmacological treatment. Angiotensin (1-7) has been focused due to its vasodilation properties and its responses to exercise, improving vascular function. Thus, stimulation of the ACE2/Ang (1-7)/Mas axis has been gaining ground as a prospective clinical means to attenuate cardiovascular diseases such as hypertension by modulating RAS activity. This review focuses on the vasoactive peptides from the RAS, their responses to exercise and possible trends for pharmacological development. In several cases where exercise training is not achievable, cardiovascular drug therapy with vasodilator peptides may possibly be an option.

Coronary artery disease (CAD) arising from atherosclerosis remains the most common cause of death and morbidity worldwide, although its risk factors, such as hypertension, dyslipidemia, and diabetes, have been individually treated with increasingly improved outcomes. Therefore, it is important to develop diagnostic and therapeutic windows for CAD. Many classical vasoactive hormones, inflammatory cytokines, and oxidative products have been implicated as potential biomarkers. Our recent studies have shown that high levels of the pro-atherogenic vasoactive agents, serotonin and urotensin II, which are potent vasoconstrictors, can be used as biomarkers for CAD. In subsequent trials, we unraveled anti- and pro-atherogenic roles for more recently identified peptides. Anti-atherogenic peptides include the adipocytokine adiponectin, the neuronal growth factor heregulin-βl (neuregulin-1 type I), the incretin hormone, glucagon-like peptide-1 (GLP-1), and a peptide recently identified by an in silico approach, salusin-α. Atherogenic roles have been demonstrated by cellular, animal, and clinical experiments, which indicate that human adiponectin, heregulin-β1, GLP-1, and salusin-α attenuate the development of atherosclerotic lesions by suppressing macrophage foam cell formation via down-regulation of acyl-CoA:cholesterol acyltransferase-1. Circulating levels of these peptides in the blood are markedly decreased in CAD patients compared with those in non-CAD patients. Receiver operating characteristic curve analyses have shown that salusin-α is the most useful biomarker for detecting CAD among the four peptides examined. Therefore, salusin-α, alone or in various combinations with heregulin-β1, adiponectin, and/or GLP-1, is a candidate biomarker for predicting CAD. Further, anti-atherogenic peptides could potentially serve as useful therapeutic targets for atherosclerotic cardiovascular diseases.

Lectins are a group of proteins which could recognize different sugar structures and specifically initiate reversible binding with them. Lectins are universally expressed in different organisms and undertake important biological roles. Understanding of their inherent roles and mechanisms that they employ has inspired researches with new ideas and applications. For example, along with the revelation of their anti-insect function, plant lectins exhibit great potential in agriculture. In human beings, lectins shoulder great missions in cell communication, differentiation and vesicle trafficking etc., aberrant expression of lectins is always associated with diseases. Mannan-binding lectin deficiency leads to immune disorder and liver sinusoidal endothelial cell lectin is involved in colorectal carcinoma liver metastasis. In this review, we present two contradictory roles of lectins in human cancer: the promotive roles of homologous lectins and suppressive roles of heterologous lectins in cancer development. Hopefully, this review will facilitate a better understanding of tumorigenesis and provide references for cancer treatment.

This review mainly summarizes results of recent studies on the anticancer activity of the multifunctional protein lactoferrin (Lf) and its derived peptide lactoferricin (Lfcin). The basic information on Lf and Lfcin, such as their sources, structures, and biological properties which favor their antitumor activity is introduced. The major anticancer mechanisms of Lf and Lfcin including cell cycle arrest, apoptosis, anti-angiogenesis, antimetastasis, immune modulation and necrosis are discussed. Other information from in vivo studies employing a mouse model is also provided. In addition, the roles of talatoferrin and delta lactoferrin, as well as improvement in drug delivery will be covered.

Living organisms are in perpetual contact with pathogenic microbes, and in encounter with parasites and predators. In order to protect themselves, they produce a variety of antimicrobial proteins and peptides. One family of such protective or defensive proteins is known as defensins, characterized by a cationic character, a low molecular mass, and an abundance of cysteine residues. Defensins from mammals and plants have been succinctly reviewed by a number of experts in this ever-growing field. This review encompasses the defensin plectasin from the saprophytic fungus Pseudoplectania nigrella as well as defensins and defensin-like peptides from invertebrate animals such as jellyfish, sponges, nematodes, crustaceans, arachnids, insects, bivalves, snails, and sea urchins. Big defensins from mollusks are mentioned together with amphioxus big defensin. The structures and activities of these defense proteins are discussed.

Cyclotides and conotoxins are two classes of disulfide-rich peptides that occur in plants and animals respectively and are the major focus of study in our laboratory. In the last three years there has been significant progress in studies of these two classes of compounds and in this article we provide an overview of the findings from our laboratory in this period. Highlights include the discovery of cyclotides in the Fabaceae and Solanaceae plant families, members of which are widely used in human nutrition, and the discovery of new classes of cyclotide precursors. These discoveries confirm the widespread distribution of cyclotides in the plant kingdom and the diversity of precursor proteins involved in their biosynthesis. Other studies have delineated the mode of action of naturally occurring cyclotides and have demonstrated the versatility of synthetic cyclotides as stable protein engineering frameworks, with applications in drug design. Conotoxins continue to be a rich source of inspiration for drug design programs, and we summarize here a range of recent studies from our laboratory focusing on the development of novel synthetic strategies and the delineation of structureactivity relationships. A major highlight was the development of an orally active cyclized conotoxin derivative that is highly efficacious in a rat model of neuropathic pain. Overall the studies described herein provide much encouragement for continuing efforts to develop peptides as drugs.