Poly dAT

Based on these monomeric building blocks a series of four structurally related poly(iminocarbonates) were synthesized carrying either no pendant chains at all [poly(Dat-Tym) ], a N-benzyloxycarbonyl group as pendant chain [poly(Z-Tyr-Tym)], a hexyl ester group as pendant chain (poly(Dat-Tyr-Hex) ], or both types of pendant chains simultaneously (poly(CTTH)] (Fig. 7). 

This series of polymers made it possible to investigate the contribution of each type of pendant chain separately. Poly(Dat-rym), the polymer carrying no pendant chains at all, was virtually insoluble in all common organic solvents. Due to its thermal instability in the molten state, poly(Dat-Tym) could be neither compression-nor injection-molded. In this respect, the processibiUty of poly(Dat-Tym) was not improved as compared to conventional poly(L-tyrosine). 

The low thermal stability of many poly(iminocarbonates) limits the use of melt fabrication techniques such as injection molding or extrusion. For example, among all six polymers tested, only poly-(Dat-Tyr-Hex) and poly(CTTH) had low enough softening points to be compression moldable without a significant degree of thermal decomposition. ... 

The corresponding polyiminocarbonates (Figure 5) were prepared first, using recently developed polymerization procedures (5). Poly(Dat-Tym iminocarbonate), the polymer carrying no pendent chains at all, was an insoluble material. Thermal processing techniques could not be used due to the low thermal stability of the polymer in the molten state. Thus poly(Dat-Tyr iminocarbonate) was a virtually non-processible material without practical applications. 

The presence of a stiff benzyloxycarbonyl group in Z-Tyr-Tym did not significantly improve the processibility or solubility of the corresponding polyiminocarbonate Poly(Z-Tyr-Tym iminocarbonate), like poly(Dat-Tym iminocarbonate), was an insoluble, and nonprocessible material. On the other hand,... 

Whereas the tensile strength was not a sensitive function of the monomer structure, the tensile modulus (Young s Modulus) was clearly related to the monomer structure. This is expected since the tensile modulus is a measure of the polymer s resistance to deformation and is related to the "stiffness" of a polymeric material. The highest tensile modulus (22,000 kg/cm2,2.2 GPa) was measured for poly(BPA iminocarbonate). Replacement of BPA by Dat-Tyr-Hex reduced the tensile modulus significantly. This observation can possibly be attributed to the presence of the long hexyl ester pendent chain in Dat-Tyr-Hex. Generally, the polyiminocarbonates were somewhat "stiffer" than the corresponding polycarbonates. Thus, the tensile moduli of poly(Dat-Tyr-Hex iminocarbonate) and poly(Dat-Tyr-Hex carbonate) were 16,300 kg/cm2 (1.6 GPa) and 13,900 kg/cm2 (1.3 GPa) respectively. 

When films of poly(Dat-Tyr-Hex carbonate) were exposed to strongly alkaline conditions (1 M NaOH at 37 C), a rapid decrease in the weight of the devices was seen. The thickness of the films decreased steadily, while the molecular weight of the intact core of the polymer matrix remained virtually unchanged. These... 

Poly(Dat-Tyr-Hex carbonate) is a slowly degrading, strong and ductile material. This material may be applicable in situations where a mechanical support function is needed for an extended period of time such as in small bone fixation devices (bone pins or screws). The reproducible fabrication of such devices by injection molding is particularly easy due to the amorphous character of poly(Dat-Try-Hex carbonate). 

The existence of differential reactivity for various sites suggests the possibility that energy absorbed at one site on the chain may be transferred down the chain until it localizes in a site with an unusually high cross section for reaction. Shulman, Gueron, and Eisinger154 claim that energy absorbed in poly dAT at the excited singlet level is transferred to a common excimer between A and T, whence it crosses to a triplet triplet excitons have been observed in poly A with a jump time of 10"8 to 10 10 sec. 

Thymidine phosphate and cytidine phosphate do not phosphoresce in a rigid ethylene glycol-water glass at 77°K109 when directly excited, but thymidine which has lost its proton at Nx does have a triplet which phosphoresces with a decay time of 0.50 sec at high pH uridine also fluoresces with a similar decay time. The quenching of purine fluorescence and appearance of T" fluorescence in UV-irradiated DNA and poly dAT (as well as U" fluorescence in poly rAU) was attributed by Rahn et al.109 to proton transfer from thymine to adenine. This quenches adenine fluorescence and enhances thymine fluorescence. 

The close correspondence of the DNA absorption spectrum with that of a mixture of mononucleotides of the same composition illustrates the weak nature of the interactions between neighboring purine and pyrimidine bases guanine (G), cytosine (C), adenine (A), and thymine (T) at an interplanar separation of 3.36 A in the unexcited double-helical configuration. On the other hand the structureless fluorescence band of (calf-thymus) DNA is red-shifted by 3500 cm-1 from the fluorescence spectral origin of the mononucleotides it closely resembles the fluorescence spectrum of the dinocleotide ApT (and of poly dAT) and is accordingly identified131 with the fluorescence... 

Narrower specificities have been obtained with antibodies to some unusual helical structures. Poly(dG)-poly(dC) induces antibodies specific for the immunogen and unreactive with other deoxyribonucleotide polymers, such as poly(dAT) or native DNA. Double-helical polyribonucleotides with modified furanoses, such as poly(A)-poly(2 -0-methylU), induce antibodies that react with a number of polymers bearing 2 -furanose substitutions (such as methyl or ethyl groups on either the purine or pyrimidine-containing strand). Poly(G)-poly(C) induced antibodies of narrow specificity in our studies, but Lacour and co-workers obtained anti-poly(G)-poly(C) that cross-reacted with several forms of viral RNA. ... 

Fig. 10.1. Resolution of the low-molecular weight polynucleotide homologues by polyacrylamide gel electrophoresis a) polyriboadenylie acid after degradation with kidney exonuclease. Samples, run on a 12% gel correspond to incubation with the enzyme under various conditions and for dilTering times (Philippsen and Zachau 1972a) b) pancreatic deoxyribonuclease partial digest of poly (dAT), alternating double helical polymer, run in 22% cylindrical gel (Elson and Jovin 1969).

The density, p, of a double stranded DNA molecule, and hence its position in the gradient, depends primarily on its nucleotide composition (eq. 2.2 gives p= 1.660+0.098 (GC)). The relation does not hold for DNAs containing glucosylated, methylated or other modified residues, nor for DNAs of very simple sequence such as synthetic polynucleotides, crab poly dAT (Wells et al. 1970) and centromeric DNA. Single stranded DNA is denser than double stranded DNA and isopycnic centrifugation can be used to separate them. 

The results obtained by various workers employing these several techniques are not in total agreement. It seems clear, however, that the presence of deoxyguanosine residues in DNA is required for binding of Actino-mycin D. Anthracyclines can complex with poly dAT and poly dGdC however, binding of nogalamycin may be favored by dAT pairs while that of daunomycin is not. The presence of cations (Mg" or Cs" ) may play a role in complex formation between the chromomycin antibiotics and DNA. 

Figure 2.3. Differential melting curves obtained with poly (dAT dAT) (solid circles), poly (dA dT) (open squares), mitochondrial (open circles) and nuclear DNA from wild-type strain B (solid squares). The ordinate, Y, indicates the increment in relative absorbance per degree of poly (dA dT) had a value...

Poly[d(A-T)] or poly(dA-dT) was originally [13] termed poly dAT. While this has the advantage of brevity, it has proven ambiguous (see footnote ) in other situations and is inconsistent with the general principles of polymer symbolism e.g. [5]). Hence, its use is not recommended. 

---