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Title: Crystal structures of ‘ALternative Isoinformational ENgineered’ DNA in B-form

The first structural model of duplex DNA reported in 1953 by Watson & Crick presented the double helix in B-form, the form that genomic DNA exists in much of the time. Thus, artificial DNA seeking to mimic the properties of natural DNA should also be able to adopt B-form. Using a host–guest system in which Moloney murine leukemia virus reverse transcriptase serves as the host and DNA as the guests, we determined high-resolution crystal structures of three complexes including 5′-CTTBPPBBSSZZSAAG, 5′-CTTSSPBZPSZBBAAG and 5′-CTTZZPBSBSZPPAAG with 10 consecutive unnatural nucleobase pairs in B-form within self-complementary 16 bp duplex oligonucleotides. We refer to this ALternative Isoinformational ENgineered (ALIEN) genetic system containing two nucleobase pairs (P:Z, pairing 2-amino-imidazo-[1,2-a]-1,3,5-triazin-(8H)-4-one with 6-amino-5-nitro-(1H)-pyridin-2-one, andB:S, 6-amino-4-hydroxy-5-(1H)-purin-2-one with 3-methyl-6-amino-pyrimidin-2-one) as ALIEN DNA. We characterized both position- and sequence-specific helical, nucleobase pair and dinucleotide step parameters ofP:ZandB:Spairs in the context of B-form DNA. We conclude that ALIEN DNA exhibits structural features that vary with sequence. Further,Zcan participate in alternative stacking modes within a similar sequence context as captured in two different structures. This finding suggests that ALIEN DNA may have a larger repertoire of B-form structures than natural DNA.

This article is part of the theme issue ‘Reactivity and mechanism in chemical and synthetic biology’.

 
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Award ID(s):
1939086
NSF-PAR ID:
10476431
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
Philosophical Transactions of the Royal Society B
Date Published:
Journal Name:
Philosophical Transactions of the Royal Society B: Biological Sciences
Volume:
378
Issue:
1871
ISSN:
0962-8436
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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