Modification of Existing Structures

The first example of a rational design of new bio-mimetic dyes used the interaction between horse liver alcohol dehydrogenase (ADH) and analogues of the textile dye Cibacron Blue F3G-A (Figure 7). It had been established that the parent dye binds in the NAD+ -binding site of the enzyme, with the an-thraquinone, diaminobenzene sulfonate and triazine rings (rings A, B and C, respectively, in Figure 7) apparently adopting similar positions to those of the adenine adenosine ribose and pyrophosphate groups of NAD-. The anthraquinone ring (A) binds in a wide apolar fold that constitutes, at one end, the adenine bridging site, while the bridging ring (B) is positioned such that its sulfonate group interacts with the guanidinium side chain of Arg271 (Figure 8). Ring C binds close to where the pyrophosphate bridge of the coenzyme binds with the reactive triazinyl chlorine adjacent to the nicotinamide ribose-binding site. The terminal ring (D) appears to be bound in a fold between the catalytic and coenzyme binding domains, with a possible interaction of the sulfonate with the side chain of Arg369. The binding of dye to horse liver ADH resembles ADP binding but differs significantly at the nicotinamide end of the molecule with the mid-point position of ring D displaced from the mid-point position of the nicotinamide ring of NAD + by about 1 nm. Consequently a number of terminal-ring analogues of the dye were synthesized and characterized in an attempt to improve the specificity of dye binding to the enzyme. Table 4 lists some of the analogues made by substituting -R in the D ring (Figure 7), together with their dissociation constants. These data show that small substituents bind more tightly than bulkier groups, especially if substituted in the o- or m-positions with a neutral or anionic group. Further inspection of the computer model given as Figure 8 showed that the dye analogues were too short and rigid to bind to horse liver ADH in an identical manner to the natural coenzyme, NAD+. Consequently analogues of the parent dye were designed and synthesized with central spacer functionalities to increase the length and flexibility of the molecule (Figure 9). This product proved to be some 10 times superior to any previously synthesized compound. This work provided the first proof that rationally designed molecules could be converted into stable, inexpensive, chromatographic media, while providing the most remarkable separations.

Solar Panel Basics

Solar Panel Basics

Global warming is a huge problem which will significantly affect every country in the world. Many people all over the world are trying to do whatever they can to help combat the effects of global warming. One of the ways that people can fight global warming is to reduce their dependence on non-renewable energy sources like oil and petroleum based products.

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