Protein catenane

To be comprehensive, it should also be mentioned that besides the unique example of the polymeric catenane 72, there exist numerous examples of DNA catenanes [34, 50, 51, 69-73] and a few examples of protein catenanes [74]. However, these aspects are beyond the scope of this section and are treated in Chapter 12. 

With the exception of DNA catenanes and protein catenanes, and despite various synthetic attempts, only one polymeric catenane structure, i.e. the catenated block copolymer 72, is known [31]. Evidently, the fact that the two constitutive cyclic polymers have two different chemical structures greatly facilitates the syn-... 

Fig. 10.2-12 Synthesis of a protein catenane based on the p53 tetramerization domain.

Figure 46. Electron micrograph of a Rec-A-protein-coated catenane produced by Tn3 resol vase, shadowed at an angle of 7° with carbon platinum. The scale bar equals 1000 A (120). (Reproduced by kind permission from Nature, Vol. 304, 559. Copyright 1983 by Macmillan Journals, Ltd.)...

In a recent paper, Krasnow and co-workers (120) applied a Rec A protein coating to DNA knots and catenanes to enhance visualization of the helical DNA segments and, in particular, to determine the absolute handedness of the knots. The Rec A protein is known to bind cooperatively to duplex DNA, forming a stiffened complex about 100 A in diameter in the presence of ATPase (121). 

Interestingly, the dumbbell component of a molecular shuttle exerts on the ring motion the same type of directional restriction as imposed by the protein track for linear biomolecular motors (an actin filament for myosin and a microtubule for kinesin and dynein).4 It should also be noted that interlocked molecular architectures are largely present in natural systems—for instance, DNA catenanes and rotaxanes... 

So, when either replication fork encounters a functional Tus-Ter complex, it halts the other fork halts when it meets the first (arrested) fork. The final few hundred base pairs of DNA between these large protein complexes are then replicated (by an as yet unknown mechanism), completing two topologically interlinked (catenated) circular chromosomes (Fig. 25-17b). DNA circles linked in this way are known as catenanes. Separation of the catenated circles in E. coli requires topoi-somerase IV (a type II topoisomerase). The separated chromosomes then segregate into daughter cells at cell... 

The discovery that DNA forms catenanes and knots, some of them extremely complex, initiated a new field of research which has been called Biochemical Topology [21]. In 1967, Vinograd and co-workers detected in HeLa cell mitochondria isolable DNA molecules that consist of independent, double-stranded, closed circles that are topologically interlocked or catenated like the links in a chain [22, 23]. A few years later, catenanes had been observed everywhere that circular DNA molecules were known [24] and the first knot was found by Liu and coworkers in single-stranded circular phage fd DNA treated with Escherichia coli co-protein [25]. In 1980, knots could also be generated in double-stranded circular DNA [26]. 

A chromophore such as the quinone, ruthenium complex, C(,o. or viologen is covalently introduced at the terminal of the heme-propionate side chain(s) (94-97). For example, Hamachi et al. (98) appended Ru2+(bpy)3 (bpy = 2,2 -bipyridine) at one of the terminals of the heme-propionate (Fig. 26) and monitored the photoinduced electron transfer from the photoexcited ruthenium complex to the heme-iron in the protein. The reduction of the heme-iron was monitored by the formation of oxyferrous species under aerobic conditions, while the Ru(III) complex was reductively quenched by EDTA as a sacrificial reagent. In addition, when [Co(NH3)5Cl]2+ was added to the system instead of EDTA, the photoexcited ruthenium complex was oxidatively quenched by the cobalt complex, and then one electron is abstracted from the heme-iron(III) to reduce the ruthenium complex (99). As a result, the oxoferryl species was detected due to the deprotonation of the hydroxyiron(III)-porphyrin cation radical species. An extension of this work was the assembly of the Ru2+(bpy)3 complex with a catenane moiety including the cyclic bis(viologen)(100). In the supramolecular system, vectorial electron transfer was achieved with a long-lived charge separation species (f > 2 ms). 

Peptide ligation strategies used so far have mainly been used for protein total synthesis and protein engineering purposes. The ability to prepare perfectly mono-disperse and relatively high molar mass peptides with precise control over the a-amino acid sequence could also afford unprecedented opportunities for the development of novel biologically-inspired supramolecular architectures and materials. As a final, recent, example, the preparation of a protein[2]catenane using NCL is shown in Figure 6.6.5 [34]. 

Fig. 6.6.5. Synthesis of a protein[2]catenane using native chemical ligation. (Adapted from Ref. [34]).

Toroidal coils, knots and catenanes. Supercoils in DNA need not physically exist as interwound supercoils. The negative supercoils can exist as left-handed toroidal coils, which topologically satisfy the requirement for W. Although in a toroidal coil the helix does not cross itself in the fashion of an interwound supercoil, it does cross itself in the plane of the toroidal coil. The organization of DNA in nucleosomes in eukaryotes involves the toroidal coiling of the DNA around proteins. 

Anion-Directed Assembly, p. 51 Enzymes Characteristics and Mechanisms, p. 554 Hydrogen Bonding, p. 658 Molecular Squares, Boxes, and Cubes, p. 909 Molecular-Level Machines, p. 931 Protein Supramolecular Chemistry, p. 1161 Racks, Ladders, and Grids, p. 1186 Self-Assembling Catenanes, p. 1240 Self-Assembly Definition and Kinetic and TTjermot/ynam-ic Considerations, p. 1248 Self-Assembly in Biochemistiy, p. 1257 The Template Effect, p. 1493... 

Nanocasting Strategies and Porous Materials, p. 950 Protein Supramolecular Chemistry, p. 1161 Self-Assembling Catenanes, p. 1240 Self-Assembly in Biochemistry, p. 1257... 

Stoddart et al. also reported poly (bis [2]catenane) 41 based on a transition metal chelation effect (Scheme 17.13) [98]. In this case, bis[2]catenane monomer 40, prepared using the same template-directed strategy as described above [99], was mixed with CF3 SO3 Ag in acetonitrile at room temperature, and poly(bis[2]catenane) 41 was obtained after counterion exchange. GPC analysis with protein standards indicated the M of 41 to be 150 kDa, corresponding to a DP of 40. 

Rare examples of unique topologies in such systems are known. However, it was recently realized that when the analysis includes cofactors and prosthetic groups such as seen in quinoproteins or iron-sulfur cluster proteins, interesting topologies including knots and catenanes are in fact more common than previously realized. As always, in considering stereochemical phenomena, our definition of connectivity is crucial. Earlier studies had counted only the amino acids as contributing to the connectivity of the system. When cofactors are included, more complex connectivities result. 

---