"Skinny" and "fat" DNA: Two New Double Helices

Shuichi Hoshika, Isha Singh, Christopher Switzer, Robert W. Molt, Nicole A. Leal, Myong Jung Kim, Myong Sang Kim, Hyo Joong Kim, Millie M. Georgiadis, Steven A. Benner

Research output: Contribution to journalArticle

10 Scopus citations


According to the iconic model, the Watson-Crick double helix exploits nucleobase pairs that are both size complementary (big purines pair with small pyrimidines) and hydrogen bond complementary (hydrogen bond donors pair with hydrogen bond acceptors). Using a synthetic biology strategy, we report here the discovery of two new DNA-like systems that appear to support molecular recognition with the same proficiency as standard Watson-Crick DNA. However, these both violate size complementarity (big pairs with small), retaining hydrogen bond complementarity (donors pair with acceptors) as their only specificity principle. They exclude mismatches as well as standard Watson-Crick DNA excludes mismatches. In crystal structures, these "skinny" and "fat" systems form the expected hydrogen bonds, while conferring novel minor groove properties to the resultant duplex regions of the DNA oligonucleotides. Further, computational tools, previously tested primarily on natural DNA, appear to work well for these two new molecular recognition systems, offering a validation of the power of modern computational biology. These new molecular recognition systems may have application in materials science and synthetic biology, and in developing our understanding of alternative ways that genetic information might be stored and transmitted.

Original languageEnglish (US)
Pages (from-to)11655-11660
Number of pages6
JournalJournal of the American Chemical Society
Issue number37
StatePublished - Sep 19 2018

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Hoshika, S., Singh, I., Switzer, C., Molt, R. W., Leal, N. A., Kim, M. J., Kim, M. S., Kim, H. J., Georgiadis, M. M., & Benner, S. A. (2018). "Skinny" and "fat" DNA: Two New Double Helices. Journal of the American Chemical Society, 140(37), 11655-11660. https://doi.org/10.1021/jacs.8b05042