Structurally modified Watson-Crick base

Generally, most publications concerning substituent effects or other structural changes in nucleobases provide information on effects observed in the base pairs. Therefore, the most frequently studied systems are structurally modified Watson—Crick base pairs, i.e., adenine—thymine (AT) and guanine—cytosine (GC) pairs. 

A critical structural issue with the subsequent incorporation of this type of chromophore-modified nucleosides into DNA duplexes is the assumption that it forms Watson-Crick base pairs with A as the counterbase. Our concern was that the large pyrene moiety may force the nucleosides into a syn conformation. 

This non-canonical fold, established according to chemical and enzymatic structure probing, includes an extended amino acid acceptor stem, an extra large loop instead of the T-stem and loop, and an anticodon-like domain. Hence, one or several of the six modified nucleosides are required and are responsible for its cloverleaf structure. In a further study a chimeric tRNA with the sole modification of 1-methyladenosine in position 9 was synthesized it was demonstrated that this chimeric RNA folds correctly [27]. Thus, because of Watson-Crick base-pair disruption, a single methyl group is sufficient to induce the cloverleaf folding of this unusual tRNA sequence. 

The Cu " "-containing, Q-modified GNA or PNA duplex adopted a structure similar to that of duplexes made exclusively from Watson-Crick base pairs, as indicated by CD spectroscopy (36, 112). In the case of Q-PNA, only the fully complementary duplexes showed a CD spectrum in the absence or in the presence of Cu " ", suggesting that structural differences due to the presence of... 

Mass spectrometry of structurally modified DNA 13CRV2395. Metal-mediated DNA base pairing as alternatives to hydrogen-bonded Watson—Crick base pairs 12ACR2066. 

Not all the base-pairing is of the Watson-Crick variety, either. For example, G-U, U-U, and A-G base pairs are relatively common. These interactions contribute to the wide variety of structures that RNA can assume. RNA molecules also contain modified nucleosides, and in some cases, quite complicated ones. These are synthesized post-transcriptionally as part of the maturation process of RNA and serve to fine-tune RNA functions. 

Figure 13 Structures and base pairing of the modified nucleoside lysidine (k C). (a) The neutral form of lysidine. The lysidine base has a pKa of approximately 12, and therefore the base would be charged at pH = 7 along with a zwitterionic form for the side chain, (b) Protonated form of lysidine allowing pairing with A in a Watson-Crick geometry, (c) and (d) Alternative protonated forms of lysidine that would be less favorable for A-pairing.

---