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Affinity and specificity of multiple hydroxypyrrole/pyrrole ring pairings for coded recognition of DNA

White, Sarah and Turner, James M. and Szewczyk, Jason W. and Baird, Eldon E. and Dervan, Peter B. (1999) Affinity and specificity of multiple hydroxypyrrole/pyrrole ring pairings for coded recognition of DNA. Journal of the American Chemical Society, 121 (1). pp. 260-261. ISSN 0002-7863. doi:10.1021/ja9830593.

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Pairings rules have been developed to guide the design of synthetic polyamides for recognition of predetermined sequences in the minor groove of DNA. We recently reported that eight-ring hairpin-polyamides containing 3-hydroxypyrrole (Hp), imidazole (Im), and pyrrole (Py) amino acids form four-ring pairings (Im/Py, Py/Im, Hp/Py, and Py/Hp) which distinguish the four Watson-Crick base pairs in the minor groove of DNA. An Im/ Py pair distinguishes G·C from C·G and both of these from A· T/T·A base pairs. A Hp/Py specifies T·A from A·T, and both of these from G·C/C·G. The T·A selectivity of the Hp/Py pair likely arises from a combination of differential destabilization of polyamide binding via placement of Hp/Py opposite A·T or T·A, and specific hydrogen bonds between the 3-hydroxy and 4-carboxamido groups of Hp with the O2 of T (Figure 1). A general pairing rule would require the same discrimination to be observed for the recognition of multiple T·A base pairs within other sequence contexts, including A·T rich sequences. In the original report, we observed that a single Hp/Py pair replacing a Py/Py pair destabilizes an eight-ring hairpin polyamide by 5-fold for an identical match site. It remains to be determined whether consecutive Hp/Py ring pairings could target binding sites varying in their A·T base pair sequence composition without compromising polyamide affinity and sequence specificity. We report here that three consecutive Hp/Py pairs can be combined within a hairpin template to distinguish core sequence 5'-TTA-3' from 5'-TAT-3' in the DNA minor groove.

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Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1999 American Chemical Society. Received August 25, 1998. Publication Date (Web): December 17, 1998. We are grateful to the National Institutes of Health (GM-27681) for research support and National Research Service Awards to S.W. and J.W.S., J. Edward Richter for an undergraduate fellowship to J.M.T., and the HHMI for a predoctoral fellowship to E.E.B.
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NIH Predoctoral FellowshipUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
J. Edward RichterUNSPECIFIED
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Record Number:CaltechAUTHORS:20160510-092908487
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Official Citation:Affinity and Specificity of Multiple Hydroxypyrrole/Pyrrole Ring Pairings for Coded Recognition of DNA Sarah White, James M. Turner, Jason W. Szewczyk, Eldon E. Baird, and Peter B. Dervan Journal of the American Chemical Society 1999 121 (1), 260-261 DOI: 10.1021/ja9830593
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66857
Deposited By: Victoria Brennan
Deposited On:17 May 2016 23:46
Last Modified:11 Nov 2021 00:23

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