The dye replaces the unstable terminal polypeptide fragment in the packing locus

The dye replaces the unstable terminal polypeptide fragment in the packing locus. formed by assembling several distinct chemical compounds. These reagents are potentially attractive due to their unique properties and possible applications in various fields [3C13]. From the medical and biological point of view interaction of supramolecular structures with proteins is a topic of great interest, yet unfortunately our knowledge of this phenomenon remains limited. Interaction of this type is known to occur in cell membranes; however surface interaction with proteins (such as in the cell membrane) is not sufficient to facilitate biological function. Penetration of a ligand composed of assembled molecules into the protein interior seems necessary. Out of many possible supramolecular architectures rode-like or ribbon-like organization appears to be the most promising for this purpose due to the existence of partly exposed hydrophobic portions of assembled compounds, favoring adhesion. Congo red is perhaps the best recognized self-assembling dye of this type and hence commonly used as a model [14C17]. It is a known amyloid stain but it also appears to form complexes with structurally unstable proteins, such as abnormal IgG light chains derived from serum or urine of myeloma patients [18C23]. Molar excess of this dye usually attaches to proteins and while a large fraction of the bound dye may easily be removed by adsorption, some dye usually remains, suggesting penetration and anchorage within the protein body. A question therefore arises: should penetrating molecules be treated as assemblages of Pexmetinib (ARRY-614) individual units or as an integral ligand? Support for the latter interpretation is provided by studies on some foreign compounds, e.g., rhodamine B intercalating into supramolecular Congo red and penetrating, together with this dye, into a protein for which it has no affinity by itself [24]. Moreover, the observed correlation of self-assembling tendencies of different organic dyes and their capability for protein complexation strongly favors treating supramolecular liagands as coherent units [25, 26]. An integrated supramolecular ligand seems necessary to achieve penetration into the protein interior. This paper discusses some effects and implications of supramolecular Congo red complexation with proteins. Congo red Pexmetinib (ARRY-614) as a model supramolecular dye Interaction of proteins with ligands is usually limited to a binding site at a specific location in the protein molecule. Binding sites are Rabbit Polyclonal to RAB31 commonly found as cavities in the protein body facilitating contact of the ligand with the Pexmetinib (ARRY-614) hydrophobic interior and separating the ligand from Pexmetinib (ARRY-614) direct dissociation pressure of the surrounding water solution. The specificity and strength of interaction which allows ligand-protein complexation is due to the specific shape of the binding site accommodating the ligand as well as to proper distribution of binding groups. The strength of nonspecific low-contact interaction of organic compounds outside the binding site is generally insufficient to stabilize ligation, even if penetration into the protein interior is occasionally possible. There is, however, an exception to this rule. It concerns self-assembled molecules creating rode-like or ribbon-like supramolecular structures. They are usually formed by elongated, planar aromatic ring-containing organic molecules with (possibly) symmetric distribution of charges in the molecule. Congo red and related dyes are an example (Fig.?1) [27C33]. Theoretical calculations enable modeling of such supramolecular structures, based initially on semi-empirical techniques and then using ab initio parameterization [17, 27]. In contrast to the molecular organization of supramolecular micellar structures with a standard globular shape, where the hydrophobic portions of amphipatic molecules are basically hidden in the micelle, fibrillar structures allow significant exposure, promoting adhesion. This property is enhanced by structural plasticity because of non-covalent stabilization further. Bits of such ribbon-like supramolecular buildings consisting of many or more set up molecules have already been verified to penetrate into proteins and bind as one ligands. -plates in protein seem to be the most preferred acceptor [26, 34C36]. Dye ligands Pexmetinib (ARRY-614) penetrate among the polypeptide strands of -plates preferentially. Replacement of minimal steady strand (from the packaging locus) to create area for the dye ligand is normally a frequently noticed sensation (Fig.?2) [37, 38]. Well-packed protein are.