Watson-Crick hydrogen bonds derivatives

Figure 4. Length (A) of Watson-Crick hydrogen bonds in CGCGAATTCGCG with T7 replaced by ring-saturated thymine derivatives. (Reproduced with permission from ref. 30. Copyright 1994 New York Academy of Sciences)...

In agreement with the chemomimetic concept as defined by Eschen-moser, the panel of enzymatic transformations for the biosynthesis of purines that we currently observe in the cell can be hypothesized to have evolved from primitive chemical processes [48-50]. 2-Carbonitrile and 2-carboxamide AICA and AICN derivatives, respectively, were also used as intermediates for the synthesis of adenine 1 and 8-substituted adenines 7 and 8 [51]. In principle, purine derivatives 7 and 8 may pair with pyrimidine bases by formation of Watson-Crick or Hoogsteen hydrogen bond interactions. 

The discovery of these base pairs, which imply the double helical structure of DNA, stimulated a series of crystal structural studies not only of complexes of purines and pyrimidines, but of other complexes involving related molecules and their derivatives. Although we can formulate a large number of possible heterocombinations in matrix form, as shown below these complexes are reluctant to crystallize even when there is spectroscopic evidence of hetero-complex formation in solution. This is presumably because self-(homo)-association is energetically more favorable and only in rare cases were crystals of hetero complexes actually formed. Because of their three hydrogen bonds, G-C complexes form and crystallize more readily. There have been many attempts to crystallize the Watson-Crick A-U base pair, but none was successful and it only formed when the dinucleoside phosphate adenylyl-3,5,-uridine (ApU [536]) or higher oligomers were crystallized (see Part III, Chapter 20). 

Non-peptide self-assembly stractures for cell immobilization can also be created using Watson-Crick base pairing principle. Four-arm (star-shaped) PEG end terminated with thiol thymine (T-SH) and thiol adenine (A-SH) was synthesized using maleimide via Michael-type addition reaction, which formed hydrogel via intermo-lecular hydrogen bonding of nucleotide base pairs. This hydrogel was successfully used to encapsulate adipose-derived stem cells (ASCs) [69],... 

Callahan et al. have used xanthine and its methylated derivatives as models for studying the two motifs [82, 83]. For the 7-methylxanthine dimer, they observed hydrogen bonding on the N3H position, suggesting three possible combinations, one that is reverse Watson-Crick type and two that are reverse Hoogsteen type. For the 3-7-dimethylxanthme dimer, they observed a stacked structure, as determined by the free NIH stretch frequency. For trimethylxanthine dimers they inferred a stacked structure as well. 

Figure 19.6 Arrangement of the three consecutive base pairs G2-C71, G3-U70, and G4-C69 a) in the starting structure (as created with the BIOPOLYMER module of INSIGHT II) obtained from a regular Watson-Crick A-RNA duplex with a G3-C70 base pair after subsequent replacement of the C70 residue by a uridine. No further adjustment of the U70 base position has been made and hence no correct hydrogen bonding pattern is found b) in the final (average) structure derived from relaxation matrix analysis of the 300 ms NOESY spectrum using the IRMA procedure [45] and restrained molecular dynamics calculation. Note that G3 and U70 now are forming a regular base pair. The bases G3 and U70 are indicated by thick lines.

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