Expanding the Pool of Multicomponent Crystal Forms of the Antibiotic 4-Aminosalicylic Acid: The Influence of Crystallization Conditions

2017 ◽  
Vol 17 (12) ◽  
pp. 6417-6425 ◽  
Author(s):  
Vânia André ◽  
Oleksii Shemchuk ◽  
Fabrizia Grepioni ◽  
Dario Braga ◽  
M. Teresa Duarte
2017 ◽  
Vol 58 (1) ◽  
pp. 67-74 ◽  
Author(s):  
O. Yu. Tkacheva ◽  
I. G. Brodova ◽  
P. A. Arhipov ◽  
Yu. P. Zaikov

2014 ◽  
Vol 70 (6) ◽  
pp. 1669-1679 ◽  
Author(s):  
Fang Zhang ◽  
Masaru Tsunoda ◽  
Yuji Kikuchi ◽  
Oliver Wilkinson ◽  
Christopher L. Millington ◽  
...  

N-Nitrosation of glycine and its derivatives generates potent alkylating agents that can lead to the formation ofO6-carboxymethylguanine (O6-CMG) in DNA.O6-CMG has been identified in DNA derived from human colon tissue and its occurrence has been linked to diets high in red and processed meats, implying an association with the induction of colorectal cancer. By analogy toO6-methylguanine,O6-CMG is expected to be mutagenic, inducing G-to-A mutations that may be the molecular basis of increased cancer risk. Previously, the crystal structure of the DNA dodecamer d(CGCG[O6-CMG]ATTCGCG) has been reported, in whichO6-CMG forms a Watson–Crick-type pair with thymine similar to the canonical A:T pair. In order to further investigate the versatility ofO6-CMG in base-pair formation, the structure of the DNA dodecamer d(CGC[O6-CMG]AATTTGCG) containingO6-CMG at a different position has been determined by X-ray crystallography using four crystal forms obtained under conditions containing different solvent ions (Sr2+, Ba2+, Mg2+, K+or Na+) with and without Hoechst 33258. The most striking finding is that the pairing modes ofO6-CMG with T are quite different from those previously reported. In the present dodecamer, the T bases are displaced (wobbled) into the major groove to form a hydrogen bond between the thymine N3N—H and the carboxyl group ofO6-CMG. In addition, a water molecule is bridged through two hydrogen bonds between the thymine O2atom and the 2-amino group ofO6-CMG to stabilize the pairing. These interaction modes commonly occur in the four crystal forms, regardless of the differences in crystallization conditions. The previous and the present results show thatO6-CMG can form a base pair with T in two alternative modes: the Watson–Crick type and a high-wobble type, the nature of which may depend on the DNA-sequence context.


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