Editorial [ Adhesion Molecules and Drug Targeting Executive Editor: Seetharama D.S. Jois ]

Cell adhesion molecules form a large group of proteins that perform several functions. These adhesion molecules can be broadly divided into families on the basis of their structure, function and duration of cell-cell interactions. A majority of adhesion molecules can be grouped into integrins, cadherins, selectins and immunoglobulin superfamilies. Modulation of cell adhesion is essential to inhibit tumor metastasis, suppress the immune response in autoimmune diseases and for improving drug delivery through biological barriers. Blocking the adhesion molecular interaction or modulation of adhesion molecules consequently produces biological effects of therapeutic value, making adhesion molecules attractive candidates for drug-design. Thus, the study of adhesion molecular interaction has been an interest among several researchers around the world. The fruitful efforts of research in this area are evident from the approved drugs in the market. For example, Cilengitide, an RGD based molecule targeting integrin has been developed as an anti-angiogenesis agent. Although, cell adhesion molecules were known for nearly two decades, the details of their structure and function were not well understood. During the past ten years 3D structures of several adhesion molecules were elucidated and the modes of interactions with their ligand were proposed. In this issue of Current Pharmaceutical Design, we are bringing out eight review articles on adhesion molecules by experts in this area. These articles provide insight into the basic mechanisms of protein-protein interactions at cell surface, the 3D structure of the proteins as well as several ligands that were designed for drug targeting, as imaging agents or as biomaterials. The topics covered are at the interface of biotechnology, structural biology and medicinal chemistry. Hence, it will be of great interest to biologists, clinicians and pharmaceutical scientists. Among the cell adhesion molecules, integrins are well understood. In the first article, Kessler and coworkers [1] discuss the details of integrin targeting for drug design, biomaterial and imaging. Special preference is given to state-of-the-art structure function relationship and RGD-based ligands to target the integrins. In another article, Lu and co workers [2] discuss the RGD-based templates for toxins and drug design. Another major integrin family receptors are Leukocyte Function associated antigen (LFA) molecules expressed on T-cells. LFA-1 has been a target for drug design for several years. Its counter receptor on the target cell is intercellular adhesion molecule (ICAM-1). These molecules have been shown to be important in autoimmune and inflammatory diseases. In the article by Giblin and Lemieux [3], detailed structure of LFA-1 and its interaction with ICAM-1 is discussed. Several new and on going ligands of LFA-1/ICAM-1 as drug targets for inflammatory and autoimmune diseases are presented. An article by our group [4] (Jois and coworkers) discusses the possible peptide ligands that are targeted to another set of adhesion molecules CD2 and LFA-3. Cadherins participate in structural integrity of cells and form important barriers such as the blood-brain barrier. Siahaan and coworkers [5] discuss the structural aspects of forming these important junctions and possible drug targeting for delivery of drugs across the blood-brain barrier. Articles by Mrowietz and Boehncke [6]; Bewick and Lafrenie [7]; Syrigos and Karayiannakis [8] cover the different adhesion molecules and their importance in inflammatory diseases and cancer. There is no doubt that adhesion molecules are attractive targets because of their importance in several stages of auto-immune and inflammatory diseases and blood-brain barrier junctions. The lead compounds and drug candidates described in this issue represent novel compounds designed to treat several chronic diseases. We hope that the articles presented in this issue will provide a summary of the state-of-the-art in the drug design area. These articles highlight the fact that research on adhesion molecules spans across several key disciplines including biotechnology, medicinal chemistry, structural biology and rational drug design. Success in such multidisciplinary research warrants close collaborations among clinicians, pharmaceutical scientists and basic biologists. Indeed, such research endeavors promise to yield several therapeutically useful agents in the coming decade. References [1] Meyer A, Auernheimer J, Modlinger A, Kessler H. Targeting RGD Recognizing Integrins: Drug Development, Biomaterial Research, Tumor Imaging and Targeting. Curr Pharm Design 2006; 12(22): 2723- 2747. [2] Lu X, Lu, D, Scully MF, Kakkar VV. Integrins in Drug Targeting-RGD Templates in Toxins. Curr Pharm Design 2006; 12(22): 2749-2769.......