The use of coiled-coil proteins in drug delivery systems.
The coiled-coil motif is found in approximately 10% of all protein sequences and is responsible for the oligomerization of proteins in a highly specific manner. Coiled-coil proteins exhibit a large diversity of function (e.g. gene regulation, cell division, membrane fusion, drug extrusion) thus demonstrating the significance of oligomerization in biological systems. The classical coiled-coil domain comprises a series of consecutive heptad repeats in the protein sequence that are readily identifiable by the location of hydrophobic residues at the 'a' and 'd' positions. This gives rise to an alpha-helical structure in which between 2 and 7 helices are wound around each other in the form of a left-handed supercoil. More recently, structures of coiled-coil domains have been solved that have an 11 residue (undecad) or a 15 residue (pentadecad) repeat, which show the formation of a right-handed coiled-coil structure. The high stability of coiled coils, together with the presence of large internal cavities in the pentameric coiled-coil domain of cartilage oligomerization matrix protein (COMPcc) and the tetrameric right-handed coiled coil of Staphylothermus marinus (RHCC) has led us and others to look for therapeutic applications. In this review, we present evidence in support of a vitamin A and vitamin D(3) binding activity for the pentameric COMPcc molecule. In addition, we will discuss exciting new developments which show that the RHCC tetramer is capable of binding the major anticancer drug cisplatin and the ability to fuse it to an antigenic epitope for the development of a new generation of vaccines.
McFarlane
Ainsley A
AA
Department of Chemistry, University of Manitoba, 144 Dysart Road, Winnipeg, Manitoba, Canada R3T 2N2. umwinte9@cc.umanitoba.ca
Orriss
George L
GL
Stetefeld
Jörg
J
D020816:Amino Acid Motifs; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D064236:Cartilage Oligomeric Matrix Protein; D002762:Cholecalciferol / Q000378:metabolism; D002945:Cisplatin / Q000378:metabolism; D016503:Drug Delivery Systems; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D064235:Matrilin Proteins; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D055672:Static Electricity; D014801:Vitamin A / Q000378:metabolism
D019496:Cancer Vaccines; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D011506:Proteins; C577553:TSP5 protein, human; D014801:Vitamin A; D002762:Cholecalciferol; D002945:Cisplatin