Mini Reviews in Medicinal Chemistry - Volume 2, Issue 4, 2002

In order to gain a therapeutic response after mucosal administration peptide drugs have to permeate the absorption membrane based on the mucus layer (I) and the epithelial tissue (II ) in significant quantities. The peptide drug transport across the membrane can be improved by the use of mucolytic agents and the permeation enhancers. The generation of novel, more potent permeation enhancers, based on an improve Read More

Antisense oligonucleotides are promising therapeutical agents for numerous diseases resulting from overexpression of genes, expression of mutant genes and viral infections. As most oligonucleotides are polyanions they can not readily pass cellular membranes in adequate amounts to show activity. Therefore, different types of carrier systems and modifications have been developed to enhance absorption and distribution at t Read More

Drug targeting with liposomes has been studied for over 25 years and has demonstrated its value in clinical practice. This mini review offers an overview of the design and application of liposomes for i.v. drug targeting. Two approaches are outlined: passive and active targeting. The former approach is based on liposomes with prolonged circulation and selective target localization properties, while in the latter approach speci Read More

Animals and plants defend themselves against pathogenic micro-organisms by the rapid mobilization of polycationic helical amphipathic peptides. Interactions with membranes induce optimal orientation and mutual structural changes, allowing for example to form transbilayer ion channels or pores whose properties are compared in this review. Physicochemical studies of peptide-lipid interactions provide attractive approaches Read More

This review focuses on the properties of ferric iron surface receptors of Gram negative bacteria. We discuss the different strategies to acquire iron, and the fundamental role of these receptors in pathogenicity. The structure of some of these receptors, iron transport and regulation mechanisms are presented here.

The oscillatory nature of the intracellular calcium signal has been recognized as soon as the methodological developments allowed us to record calcium fluctuations at the single cell level. While the principal mechanisms responsible for the generation of these oscillations have been partially resolved, more attention has been recently focused on signal decoding and more particularly on the role of cell structure organization in Read More

Heptahelical receptors are coupled to heterotrimeric GTP-binding proteins (G proteins) which transduce most signals through their a and bg subunits to effectors including adenylylcyclases, ion channels, phospholipases Cb, and phosphoinositide 3-kinases. The diversity of G proteins, their effectors and regulators (RGS proteins), supports the interest of these protein families as potential drug targets.

Chemokine receptors are membrane proteins that play an important role in inflammation and the cellular entry of human immunodeficiency virus type I (HIV-1). Understanding the structure-function relationship of chemokine receptor-ligand interactions and developing novel strategies to control these interactions have important implications for therapeutic intervention of human diseases such as HIV-1 infection. This articl Read More

Local anesthetics inhibit the ion channel activity of nicotinic acetylcholine receptors in a noncompetitive fashion. This inhibitory action is ascribed to two possible inhibitory mechanisms: an openchannel- blocking mechanism and / or an allosteric process where the drug binds either to the closed channel or to other nonluminal sites, respectively.

Steroid hormones may possess two distinct actions, a delayed genomic influence and the rapid nongenomic effects, which may act in concert. Nongenomic effect may be mediated by putative membrane receptors or due to allosteric interactions of steroids with membrane proteins (e.g. ionic channels), inducing rapid changes in protein / receptor / channel activation or inhibition.

Most insecticides are potent neurotoxicants that act on various neuroreceptors and ion channels. However, the major target receptors are limited to sodium channels, GABA receptors, and nicotinic acetylcholine receptors. DDT and pyrethroids act similarly on sodium channels to keep them open leading to hyperexcitation. Indoxacarb inhibits sodium channels and certain subtypes of nicotinic receptors. Dieldrin, lindane and fi Read More