Current Pharmaceutical Design - Volume 15, Issue 21, 2009

The production of new molecular entities endowed with salutary medicinal properties is a formidable challenge; synthetic molecules that can bind with high sequence specificity to a chosen target in a protein or gene sequence are of major interest in medicinal and biotechnological contexts. The general awareness of the importance of peptides in physiology and pathophysiology has markedly increased over the last few years Read More

Antimicrobial peptides (AMPs) are multi-functional peptides whose fundamental biological role in vivo has been proposed to be the elimination of pathogenic microorganisms, including Gram-positive and -negative bacteria, fungi, and viruses. Genes encoding these peptides are expressed in a variety of cells in the host, including circulating phagocytic cells and mucosal epithelial cells, demonstrating a wide range of utility in the Read More

In addition to the physical barrier of the stratum corneum, cutaneous innate immunity also includes the release of various humoral mediators, such as cytokines and chemokines, recruitment and activation of phagocytes, and the production of antimicrobial proteins/ peptides (AMPs). AMPs form an innate epithelial chemical shield, which provides a front-line component in innate immunity to inhibit microbial invasion; however, this Read More

Growth factors (GFs) are extracellular signaling polypeptides regulating cell proliferation, differentiation and survival. They exert a wide spectrum of biological activities selectively binding to and activating specific membrane receptors which then transfer the message to cell interior inducing specific biochemical pathways. GFs are especially involved in the regulation of angiogenesis, a physiological process underlining several Read More

Nicotinic acetylcholine receptors (nAChRs) are pentameric membrane-bound proteins belonging to the large family of ligandgated ion channels. nAChRs possess various binding sites which interact with compounds of different chemical nature, including peptides. Historically first peptides found to act on nAChR were synthetic fragments of snake α-neurotoxins, competitive receptor antagonists. Later it was shown that frag Read More

Regulatory peptide receptors are overexpressed in numerous human cancers. The specific receptor binding property of peptides can be exploited by their labelling with a radionuclide and their use as carriers to guide the radioactivity to the tissues expressing their specific receptors. During the past decade, radiolabelled receptor-binding peptides have emerged as an important class of radiopharmaceuticals for tumour diagnosis Read More

Phosphorylation by protein kinases is a central theme in biological systems. Aberrant protein kinase activity has been implicated in a variety of human diseases, therefore, modulation of kinase activity represents an attractive therapeutic approach for the treatment of human illnesses. Development and design of specific inhibitors for protein kinases thus became a major strategy in many drug discovery programs. Inhibi Read More

Mammalian MAPK cascades are essential for cellular signaling in response to mitogenic signals and stress-stimuli to regulate proliferation, differentiation and apoptosis. The three major MAPK cascades, ERK1/2-, JNK- and p38, maintain signaling specificity by scaffolding proteins and by specific docking interactions between pathway components. The structures mediating these interactions include the domain of versatile Read More

Rho GTPases represent a family of small GTP-binding proteins that are involved in many important cellular functions relevant to cancer including cell cytoskeleton organization, migration, transcription, and proliferation. Since deregulation of members of Rho GTPase family is often found associated with many disease states, targeting of Rho GTPases and related signaling pathways for potential therapeutic benefits has bee Read More

Protein folding in the cell is a complex process with a fine balance between productive and non-productive folding. To modulate, either up-regulating or down-regulating, the level of one specific protein with multiple approaches is possible, including the modulation of catalysed protein folding, the use of chemical and pharmacological chaperones, alteration of natural protein-protein interactions, the regulation of degrad Read More

Multiple clinical benefits have been obtained thanks to the combination of drugs targeting several steps of the HIV-1 replication. However, despite such combination therapy, complete eradication of the virus cannot be attained. Moreover, emergence of resistance observed under treatment and the lengthening life expectancy of treated patients highlight the need for new anti-HIV agents. Peptide- based compounds that exhi Read More

Most viral treatments target the virus itself, providing very specific effects and limiting side-effects on uninfected cells. However, this strategy of drug design often results in resistant viruses, especially among RNA viruses. Therefore, the focus has turned to drugs that target cellular proteins that are essential for viral replication, but not for cellular viability. Pharmacological CDK inhibitors are a prime example of this type of ap Read More