Duplex parallel

The a-anomeric form of a 2 -deoxyribose, which has the base inverted with respect to the natural P-anomeric form, can be synthesized by using the phosphoramidite method sugar modification renders the derivatives nuclease-resistant. These analogues form parallel duplexes with complementary RNA... 

Duplex, cylinders mounted in parallel on two separate frames from common crankshaft. Figure 12-5B. 

Earlier studies using thermal denaturation analysis and spectrophotomet-ric titration with TxA T and CxC-C" containing DNA triplexes showed that coralyne binds strongly to these triplexes by intercalation and does not exhibit a significant sequence-selectivity [222]. In a later study by Morau Allen et al. [217], employing DNase footprinting, thermal denaturation analysis, UV-visible spectrophotometric titrations, circular dichroism and NMR spectroscopy, showed that coralyne is fully intercalated into TxA T triplex DNA whereas in C GxC triplex, it is partially intercalated due to electrostatic repulsion between the cationic alkaloid and the protonated cytosine [217]. Kepler et al. [223] demonstrated that coralyne intercalated to parallel triplex DNA but did not intercalate to antiparallel triplex DNA. Recently Hud and coworkers [219,224] demonstrated that duplex poly(dA) poly(dT) is trans-... 

Very recently the trans- [Pt(NH3)2Cl2] isomer has been shown to promote the formation of some highly unusual multiple strand nucleic acid structures (28). A parallel-stranded DNA duplex, psPtDNA, has been prepared which incorporates a frarcs-Pt(NH3)2+ crosslink. The pla-tinated strands were synthesized through the series of reactions illustrated in Fig. 3. The initial mono-functional G N7 adduct is formed at pH 3.5 by addition of rans-[Pt(NH3)2(H20)Cl]+ to the pyrimidine-rich sequence 5 -d(T4CT4G). After the pH is increased, normal anti-parallel duplex formation occurs upon addition of the complementary purine-rich strand, 5 -d(A4GA4G). This intermediate anti-parallel stranded... 

DNA, apsPtDNA, contains an overhanging G-residue that undergoes preferential inter-duplex crosslinking (4°C over a period of 2 months) to form 3 -crosslinked complementary strands. Duplex melting and intramolecular hybridization at pH 4.2 leads to the formation of parallel stranded DNA, psPtDNA. 

Fig. 4. Possible homo-dimers of psPtDNA (A) antiparallel duplex, (B) parallel duplex, (C) quadruplex. Adapted from Ref. (28).

Fig. 5. Possible base-pairing interactions for the quadruplex homodimer. Hoogsteen pairings of the parallel stranded PtDNA duplex requires protonation of the GC pair. Adapted from Ref. (28).

PNA oligomers are synthetic DNA mimics possessing an amide backbone which are able to base pair with DNA and RNA in an anti-parallel fashion (Fig. 7) [25]. The most interesting difference between DNA and PNA is the neutral backbone possessed by PNA at physiological pH. Consequently this leads to an increased stability of the duplexes they form with DNA and PNA oligomers can therefore be shorter than corresponding ONDs when used... 

Comparison with the Crystalline Structure of A- and B-Type Starch. In the most recent crystallographic studies on the crystalline part of starch (14.15) the structure of both polymorphs are based on a parallel arrangement of left-handed double-helices. In the two observed structures the double-helices are slightly different since small variations away from the perfect six-fold symmetry are found. Nevertheless, they correspond closely to the model studied here. The essential result is that in these two structures the closest interactions between two neighboring double-helices correspond closely to the duplex described as PARA 1. 

Figure 9. Model of the polymorphic transition from the B-type to the A-type starch, in the solid state. The parallel double-helices which form the duplex are labelled 0 and 1/2 (this indicates their relative translation along the c axis). The water molecules are shown as dots.

Using the pitch, symmetry, monomer geometries and other stereochemical constraints, a number of types of molecular model can be constructed. Typical dilemmas are whether the molecular helix is left- or right-handed, whether the molecule is a single helix or coaxial double-helix (and in the later case whether the two chains in the duplex are parallel or antiparallel), or whether, if there are two or more molecules in the unit cell, the molecules are parallel or antiparallel. Solution of a structure therefore involves refinement and adjudication All candidate models are refined until the fit with the measured x-ray amplitudes or steric factors allows one model to be declared significantly superior to the others by some standard statistical test. 

Notice the particular features of this kind of ohgonucleotide the hexameric sequence is said to be self-complementary, since two identical molecules can form a duplex via Watson and Crick bases. It may also be noted from Figure 7.5 that two parallel pathways compete for the formation of the template T, namely the template-dependent, autocatalytic pathway, and the template-independent, non-autocatalytic one. This competition is the reason why the initial rate of the autocatalytic synthesis was found to be proportional to the square root of the template concentration -something that von Kiedrowski and colleagues called the square-root law of autocatalysis. As Burmeister (1998) put it ... 

Figure 5-27 Stereoscopic view of a four-stranded intercalated DNA or I-DNA formed from d(C4). Two parallel duplexes with C CH+ pairs are intercalated into each other. From Chen et al.280...

Fig. 4. Scheme of the preparation containing P-labeled phosphomonoesters at single-strand breaks. The two strands of Ti DNA duplex are schematically represented by two parallel lines and only the 5 termini are designated. After the introduction of single-strand breaks into DNA by incubation with pancreatic DNase, the phosphomonoesters formed are removed by phosphatase at 65°. The 5 termini are then labeled by incubation with polynucleotide kinase. From Weiss el al. (56). 

Several other types of backbone modification have also been proposed, which produce nuclease-resistant oligos. Of these, a-oligos have been extensively studied. In a-oligos the base is transposed from the natural P-orientation to the unnatural a-orientation to form a parallel duplex with target sequence. This parallel duplex is nuclease-resistant, but does not elicit RNase H activity (Cazenave et al., 1989). These modifications have generated limited interest and application in antisense research. 

---