Current Pharmaceutical Design - Volume 11, Issue 28, 2005

This special issue of Current Pharmaceutical Design is dedicated to cell-penetrating peptides, CPPs, their mechanisms and applications. It is divided into seven chapters in which several aspects of cell-penetrating peptides are updated. This issue was compiled in November 2004 and reflects the concise summary of CPP research in recent 10 years since the first CPP, pAntennapedia (later named penetratin) was discovered by Alai Read More

A major obstacle in the development of new therapeutic agents is the low bioavailability of hydrophilic substances. Drugs that bind to intracellular targets must penetrate the lipid bilayer surrounding the cell in order to exert their effect. A relatively new research area that addresses this problem by introducing novel transport peptides that facilitate the cellular penetration of potential drugs has emerged. These peptides p Read More

With the identification of fixation as a major source of artefacts in the cell biological research on cellpenetrating peptides (CPPs), the past two years have witnessed a dramatic development in the CPP field. At least for some of these molecules, endocytosis is now considered to be the major if not the exclusive route of cellular import. However, endocytosis comprises a variety of different pathways with very different implications fo Read More

This review focuses on two peptides, MPG and Pep-1, which facilitate the transfer of nucleic acids and proteins, respectively, into subcellular compartments. We have investigated the interactions between these two carrier peptides and model membrane systems as well as the conformational consequences of these interactions. Studies performed with lipid monolayers at the air - water interface have enabled id Read More

The review describes key aspects of the synthesis and biological activities of conjugates of oligonucleotides and their analogues with synthetic peptides, in particular aimed towards gene silencing applications. The common methods of synthesis of oligonucleotide-peptide conjugates (OPCs) and PNA-peptide conjugates (PPCs) are described, which include both total solid-phase and fragment coupling approaches. In addition, v Read More

In vivo screening of phage-displayed peptide libraries has revealed extensive molecular heterogeneity in the blood vessels of individual normal tissues and shown that pathological lesions put their signature on the vasculature. In tumors, both blood and lymphatic vessels differ from normal vessels. Moreover, the molecular changes in the vasculature parallel progression in tumor development, hence making the vessels in pr Read More

The rescent discovery of carrier peptides offers new opportunities to translocate several bioactive molecules into the cytoplasm. Previous studies have shown that human calcitonin (hCT) and selected C-terminal sequences translocate in nasal epithelium. Moreover, the hCT(9-32) fragment was found to internalize efficiently a number of substances like fluorophores, nucleic acids or the enhanced green fluorescent protein (EGFP) Read More

Non-viral gene delivery is an important approach in order to establish safe in vivo gene therapy in the clinic. Although viral vectors currently exhibit superior gene transfer efficacy, the safety aspect of viral gene delivery is a concern. In order to improve non-viral in vivo gene delivery we have designed a pharmaceutical platform called Bioplex (biological complex). The concept of Bioplex is to link functional entities via hybridisin Read More

The development of atherosclerotic lesions in the artery wall is a complex process involving the endothelium, lipid engorged macrophages (foam cells) and smooth muscle cells. In recent years it has become clear that chylomicron remnants, the lipoproteins which carry lipids of dietary origin in the blood, are strongly atherogenic, and there is increasing evidence to indicate that this is due to direct interaction of the remnant p Read More

The use of highly active antiretroviral therapy (HAART) has significantly slowed the HIV disease progression. However, adverse effects are now a limiting cause of HAART benefit in a substantial proportion of patients. Particularly hepatotoxicity which is a common complication occurring during every HAART regimen. All antiretroviral (ARV) drugs classes, Nucleoside/Nucleotide reverse transcriptase inhibitors (NRTI), non-Nucleosid Read More

Convenient strategies are needed for postmenopausal osteoporosis management. Current oral bisphosphonates are effective and generally well tolerated, but are hampered by strict dosing requirements. Less frequent dosing schedules are expected to improve adherence to therapy and hence outcomes. Ibandronate is a potent, nitrogen-containing bisphosphonate in ongoing clinical development exploring its potential to Read More