Editorial [Hot Topic: Therapeutic Potential of Peptide Motifs - Part I (Executive Editor: Jean-Claude Herve)]

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. With progresses in the analysis of whole genomes, the knowledge base in gene sequence and expression data useful for protein and peptide analysis has drastically increased. The medical need for relevant biomarkers is enormous. This is particularly true not only for many types of cancers, but also for other diseases, e.g. type 2 diabetes or cardiac diseases, which also lack adequate diagnostic markers with high specificity and sensitivity. Imaging technologies for early detection of diseases, proteomic and peptidomic multiplex techniques have markedly evolved in recent years. Peptides can indeed be regarded as ideal agents (as “magic bullets”) for diagnostic and therapeutic applications, because of their fast clearance, rapid tissue penetration, and low antigenicity, and also of their easy production, allowing innumerable biological applications. They can easily be engineered to improve their biological activities as well as their stability and their efficient delivery to specific targets. The present issue of Current Pharmaceutical Design, for which I have the honour to be Executive Guest Editor, addresses topical issues to some of these potential utilisations of peptide motifs for a variety of genetic and acquired diseases. During the past years, proofs of the fact that peptide receptors can be successfully used for in vivo targeting of human cancers, have been provided. The molecular basis for targeting grounds on the in vitro observation is that peptide receptors can be expressed in large quantities in certain tumours. The clinical impact is at the diagnostic level: in vivo receptor scintigraphy uses radiolabelled peptides for the localisation of tumours and of their metastases. Peptidic tumour targeting agents can be sub-divided into the following segments: peptide, spacer, bifunctional chelator, and radioisotope. Denise Zwanziger and Annette G. Beck-Sickinger [1] summarise the biological and chemical properties of peptide hormones and their prerequisites for use as tumour targeting agents for both diagnostic and therapeutic purposes, alone or in combination with other peptide hormones or as the carriers for cytotoxic agents. Radiolabelled peptides have emerged as an important class of radiopharmaceuticals for imaging and therapy of inflammatory diseases and malignancies. These radiopharmaceuticals, which bind with high affinity and specificity to their receptors present in these structures, have an excellent diagnostic potential for the imaging of patients with chronic inflammatory diseases or tumours. The challenge is to label bioactive peptides without affecting their receptor binding properties. Size, plasma protein binding, lipophilicity and sensitivity to proteolysis are to be considered, with biodistribution, metabolism and excretion characteristics. G. Malviya, A. Signore, B. Laganà and R.A. Dierckx [2] describe the characteristics of peptides, cytokines and monoclonal antibodies with a particular emphasis to their role for therapy decision making and follow up in different inflammatory diseases. Cell penetrating peptides (CPPs) have the promising ability to cross the plasma membranes of mammalian cells in an apparently energy- and receptor-independent fashion. Most of the currently recognised CPPs are of cationic nature and derived from viral, insect or mammalian proteins endowed with membrane translocation properties. The exact mechanism underlying this translocation remains poorly understood, but this ability is being exploited to deliver a broad range of problematic therapeutic cargos, such as proteins, DNA oligomers, antibodies, peptide-nucleic acids, imaging agents, magnetic nanoparticles and liposomes in a variety of situations and biological systems. Veerle Kersemans, Ken Kersemans and Bart Cornelissen [3] present an overview of the use of CPPs for molecular imaging and discussed the difficulties and pitfalls of their utilisation. Peptide microarray technologies, based on the high-density immobilisation of surface-bound peptides on the solid planar supports, allowing them to sense protein activity (like substrates) or to act as small molecule ligands (for potential therapeutic leads) in profiling, detection or diagnostic applications. Peptides can be rapidly synthesised as large, defined library sets, which can be installed with orthogonal or directed chemical tags for convenient immobilisation on arrays. These approaches, allowing to miniaturise, parallelise and automate high throughput screening, have emerged as one of the most prominent and revolutionary technologies currently available for multiplexed detection.