Covalent links

Maggini M, Done A, Scorrano G and Prato M 1995 Synthesis of a [60]fullerene derivative covalently linked to a ruthenium (II) tris(bipyridine) complex J. Chem. Soc., Chem. Commun. 845-6... 

Proteins are biopolymers formed by one or more continuous chains of covalently linked amino acids. Hydrogen bonds between non-adjacent amino acids stabilize the so-called elements of secondary structure, a-helices and / —sheets. A number of secondary structure elements then assemble to form a compact unit with a specific fold, a so-called domain. Experience has shown that a number of folds seem to be preferred, maybe because they are especially suited to perform biological protein function. A complete protein may consist of one or more domains. 

Quinolone-Gephalosporin Godrugs. Quinolones have been covalently linked to cephalosporins in order to generate a codmg containing one molecule of each type of antibacterial agent. An example is the fleroxacin—cefotaxime [63527-52-6] combination, Ro 23-9424 [115622-58-7] (23). 

A significant difference between pseudoirreversible inhibitors and mechanism-based inactivators is the reversibiUty of the inactivation. A complete evaluation of the mechanism involved would require evidence not only for the covalent enzyme-inhibitor complex, but also for its decomposition products and its rate of reactivation. It is often difficult to identify the active site amino acid residue covalently linked to the inhibitor because of the instabiUty of the complex. 

It seems likely, therefore, that as the bound phosphate molecule is released, the cleft starts to open and the myosin head binds to actin (Figure 14.17d). Release of ADP coincides with a conformational change that fully opens the myosin cleft, causing actin to be tightly bound, and moves the lever arm to the "down" position. Since the myosin head is now strongly bound to actin at one end and covalently linked to the myosin fibril at the other... 

The outstanding morphological feature of these rubbers arises from the natural tendency of two polymer species to separate one from another, even when they have similar solubility parameters. In this case, however, this is restrained because the blocks are covalently linked to each other. In a typical commercial triblock the styrene content is about 30% of the total, giving relative block sizes of 14 72 14. At this level the styrene end blocks tend to congregate into spherical or rod-like glassy domains embedded in an amorphous rubbery matrix. These domains have diameters of about 30 nm. 

Saturated — the condition of an organic compound in which each constituent carbon is covalently linked to four different atoms. This is generally a stable configuration (e.g., CHjCHjCHj - propane). 

The structure of any molecule is a unique and specific aspect of its identity. Molecular structure reaches its pinnacle in the intricate complexity of biological macromolecules, particularly the proteins. Although proteins are linear sequences of covalently linked amino acids, the course of the protein chain can turn, fold, and coil in the three dimensions of space to establish a specific, highly ordered architecture that is an identifying characteristic of the given protein molecule (Figure 1.11). 

Whereas the primary structure of a protein is determined by the covalently linked amino acid residues in the polypeptide backbone, secondary and higher... 

FIGURE 6.20 A disaccharide of galactose and glucose is covalently linked to the 5-hydroxyl group of hydroxylysines in collagen by the combined action of the enzymes galactosyl transferase and glucosyl transferase. 

Insulin is composed of two peptide chains covalently linked by disulfide bonds (Figures 5.17 and 6.35). This monomer of insulin is the active form that binds to receptors in target cells. However, in solution, insulin spontaneously forms dimers, which themselves aggregate to form hexamers. The surface of the insulin molecule that self-associates to form hexamers is also the surface that binds to insulin receptors in target cells. Thus, hexamers of insulin are inactive. 

Certain proteins are found to be covalently linked to lipid molecules. For many of these proteins, covalent attachment of lipid is required for association with a membrane. The lipid moieties can insert into the membrane bilayer, effectively anchoring their linked proteins to the membrane. Some proteins with covalently linked lipid normally behave as soluble proteins others are integral... 

FIGURE 9.25 Teichoic acids are covalently linked to the peptidoglycan of Grampositive bacteria. These polymers of (a, b) glycerol phosphate or (c) ribitol phosphate are linked by phosphodiester bonds. 

Many proteins found in nature are glycoproteins because they contain covalently linked oligo- and polysaccharide groups. The list of known glycoproteins includes structural proteins, enzymes, membrane receptors, transport proteins, and immunoglobulins, among others. In most cases, the precise function of the bound carbohydrate moiety is not understood. 

FIGURE 10.23 The folding of halorhodopsin with the transmembrane segments indicated. The only lysine residue in the protein is Lys , to which the retinal chromophore is covalently linked. 

Muscle glycogen phosphorylase is a dimer of two identical subunits (842 residues, 97.44 kD). Each subunit contains a pyridoxal phosphate cofactor, covalently linked as a Schiff base to Lys °. Each subunit contains an active site (at the center of the subunit) and an allosteric effector site near the subunit interface (Eigure 15.15). In addition, a regulatory phosphorylation site is located at Ser on each subunit. A glycogen-binding site on each subunit facilitates prior association of glycogen phosphorylase with its substrate and also exerts regulatory control on the enzymatic reaction. 

The 4-phosphopantetheine group of CoA is also utilized (for essentially the same purposes) in acyl carrier proteins (ACPs) involved in fatty acid biosynthesis (see Chapter 25). In acyl carrier proteins, the 4-phosphopantetheine is covalently linked to a serine hydroxyl group. Pantothenic acid is an essential factor for the metabolism of fat, protein, and carbohydrates in the tricarboxylic acid cycle and other pathways. In view of its universal importance in metabolism, it is surprising that pantothenic acid deficiencies are not a more serious problem in humans, but this vitamin is abundant in almost all foods, so that deficiencies are rarely observed. 

FIGURE 18.32 Biotin is covalently linked to a protein via the e-amino group of a lysine residue. The biotin ring is thus tethered to the protein by a 10-atom chain. It functions by carrying carboxyl groups between distant sites on biotin-dependent enzymes. 

FIGURE 21.13 The structure of mitochou-dtial cytochrome c. The heme is shown at the center of the structure, covalently linked to the protein via its two sulfur atoms (yellow). A third sulfur from a methionine residue coordinates the iron. 

FIGURE 25.10 Acetyl units are covalently linked to a serine residue at the active site of the acetyl transferase in eukaryotes. A similar reaction links malonyl units to the malonyl transferase. 

Chemistry of photoproteins (modified proteins with luminescent covalent-linked heterocyclic fragments) as interface between bioactive molecules and protein function 98PAC2085. 

Graft copolymer—A graft copolymer consists of a polymeric backbone with covalently linked lateral... 

Q A Boc-protected amino acid is covalently linked to the polystyrene polymer by formation of an ester bond (Sn2 reaction). 

The observation that addition of imidazoles and carboxylic acids significantly improved the epoxidation reaction resulted in the development of Mn-porphyrin complexes containing these groups covalently linked to the porphyrin platform as attached pendant arms (11) [63]. When these catalysts were employed in the epoxidation of simple olefins with hydrogen peroxide, enhanced oxidation rates were obtained in combination with perfect product selectivity (Table 6.6, Entry 3). In contrast with epoxidations catalyzed by other metals, the Mn-porphyrin system yields products with scrambled stereochemistry the epoxidation of cis-stilbene with Mn(TPP)Cl (TPP = tetraphenylporphyrin) and iodosylbenzene, for example, generated cis- and trans-stilbene oxide in a ratio of 35 65. The low stereospecificity was improved by use of heterocyclic additives such as pyridines or imidazoles. The epoxidation system, with hydrogen peroxide as terminal oxidant, was reported to be stereospecific for ris-olefins, whereas trans-olefins are poor substrates with these catalysts. 

Sassoon and Rabani [79, 83] constructed an intriguing photoinduced ET system in which the back ET was greatly retarded by the electrostatic repulsion between two different polycations. They prepared poly(3,3-ionene) covalently linked with Ru(bpy)f + (26) and with an iY,Af,/V, Ar -tetraalkyl-/>-phenylenediamine derivative (27). The latter is an electron donor quencher toward the photoexcited Ru(II) complex. 

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