Current Pharmaceutical Design - Volume 17, Issue 38, 2011

Broadly speaking, there are only two major structural classes of approved drugs, small molecules and protein therapeutics (also known as biologics). Small molecules typically show good stability and good pharmacological properties, but their intrinsic small size (≤100 atoms) endows them with only a modest overall surface area available to contact a protein target, which seriously limits their ability to effectively target Read More

Conotoxins are small bioactive highly structured peptides from the venom of marine cone snails (genus Conus). Over the past 50 million years these molluscs have developed a complex venom cocktail for each species that is comprised of 100-2000 distinct cysteine- rich peptides for prey capture and defence. This review focuses on an important and well-studied class of conotoxins, the α- conotoxins. These α-conotoxins a Read More

The peptides present in the venoms of marine snails are used by the snails to capture prey, but they have also attracted the interest of drug designers because of their potent activity against therapeutically important targets. These peptides are typically disulfiderich and target a wide range of ion channels, transporters and receptors with exquisite selectivity. In this article, we discuss structural and biological studies on Read More

Defensins are an important family of cationic and cysteine-rich host defense peptides that are widely distributed in plants, fungi, and animals. In mammals, defensins exert potent antimicrobial and immunomodulatory activities linking the innate and adaptive immune responses. These peptides play critical roles in health and disease as defects in their production are associated with abnormal host responses to infection, Read More

Plant defensins are cationic peptides that are ubiquitous within the plant kingdom and belong to a large superfamily of antimicrobial peptides found in several organisms collectively called defensins. The primary structure of these peptides includes 45 to 54 amino acid residues with considerable sequence variation. At the level of three-dimensional structure, they are small and globular, composed of three anti-parallel β-sheets an Read More

Cyclotides are a unique and growing family of backbone cyclized peptides that also contain a cystine knot motif built from six conserved cysteine residues. This unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Aside from the conserved residues forming the cystine Read More

This work is focused on SFTI-1, a member of the Bowman-Birk family of inhibitors. This 14 amino acid cyclic peptide exhibits several features i.e. compact rigidity, well-defined structure and small size that could result in a wide range of potential applications. Some examples of engineering of the specificity of this inhibitor along with structure - activity relationships will be discussed herein. Additionally, potential uses of STFI-1 a Read More

Transpeptidation reactions result in the formation of new peptide bonds and this can occur between two separate peptides or within the one peptide. These reactions are catalyzed by enzymes and when the N- and C-terminus of the one peptide are joined it results in the formation of cyclic proteins. Cyclization via head-to-tail linkage of the termini of a peptide chain occurs in only a small percentage of proteins but give Read More

Cystine knot miniproteins define a class of peptides in the size range of approximately 28-35 amino acid residues that often combine high chemical and biological stability with high potency and selectivity. They share a common structural motif that is defined by three intramolecular disulfide bonds that gives rise to a very stable scaffold. Members of this family cover a broad spectrum of natural bioactivities ranging from anti Read More

The knottins are extremely stable miniproteins present in many species and are able to perform various tasks. Owing to its small size and its amazing stability, the knottin structural domain is considered as an excellent scaffold for drug development. Several recent databases and web servers dedicated to or aware of knottins have appeared and are shortly described. Altogether they provide a valuable ensemble of dat Read More

Crotamine, a low molecular weight cationic polypeptide from the venom of the South American rattlesnake Crotalus durissus terrificus is a natural cell-penetrating peptide with functional versatility. The presence of nine lysine residues and three disulfide bonds renders crotamine highly compact, stable and positively charged. Topologically, crotamine adopts an ancient β-defensin fold that is found in diverse families of en Read More

Surgical resection remains the primary component of cancer therapy. The precision required to successfully separate cancer tissue from normal tissue relies heavily on the surgeon's ability to delineate the tumor margins. Despite recent advances in surgical guidance and monitoring systems, intra-operative identification of these margins remains imprecise and directly influences patient prognosis. If the surgeon had improved Read More

Inflammation and oxidative process are associated with inflammatory bowel disease (IBD). Regarding anti-inflammatory and antioxidant potentials, melatonin has been found beneficial in several experimental and clinical studies including inflammatory bowel disease (IBD). Our objective in this study is to review and evaluate all non-clinical and clinical studies on the efficacy of melatonin in IBD. All indexing databases were searc Read More

Accelerated atherosclerosis and microvascular complications are the leading causes of coronary heart disease, end-stage renal failure, acquired blindness and a variety of neuropathies, which could account for disabilities and high mortality rates in patients with diabetes. Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family. L cells in the small intestine secrete GLP-1 in response to food intake. GLP-1 n Read More