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Parallel synthesis of H-pin polyamides by alkene metathesis on solid phase

Olenyuk, Bogdan and Jitianu, Cristian and Dervan, Peter B. (2003) Parallel synthesis of H-pin polyamides by alkene metathesis on solid phase. Journal of the American Chemical Society, 125 (16). pp. 4741-4751. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20160510-081357762

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Abstract

A small library of H-pin polyamides with variable aliphatic bridge lengths (CH(2))(n)(), where n = 4-8, connecting a central Py/Py pair was prepared via parallel synthesis with Ru-catalyzed alkene metathesis on solid phase as a complexity-generating cross-linking reaction. DNA binding affinities and sequence specificities were analyzed for each member of the library to determine the optimum linker length. An H-pin polyamide with a six-methylene bridge was found to have the highest affinity to its match site with high selectivity over a 1-bp mismatch site. The relationship between the number of methylenes in the linker (CH(2))(n)() and affinity is n = 6 > 4 > 7 > 5 > 8. These results indicate that 6 followed by 4 methylene-bridged polyamides represent the optimum spacer length for the H-pin motif in the DNA minor groove. Importantly, the H-pin is competitive with hairpin polyamides with respect to affinity and specificity. The metathesis-based convergent synthetic route to H-pin polyamides expands the scope of readily available DNA recognition motifs for small molecule-based gene regulation studies.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja0213221DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja0213221PublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja0213221PublisherSupporting Information
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2003 American Chemical Society. Received November 1, 2002. Publication Date (Web): March 29, 2003. We thank the National Institutes of Health (GM-27681) for research support and a postdoctoral fellowship to B.O. (F32 GM-19788). C.J. is grateful to California Institute of Technology for a Summer Undergraduate Research Fellowship.
Funders:
Funding AgencyGrant Number
NIHGM-27681
NIH Postdoctoral FellowshipF32 GM-19788
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
Issue or Number:16
Record Number:CaltechAUTHORS:20160510-081357762
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-081357762
Official Citation:Parallel Synthesis of H-pin Polyamides by Alkene Metathesis on Solid Phase Bogdan Olenyuk, Cristian Jitianu, and Peter B. Dervan Journal of the American Chemical Society 2003 125 (16), 4741-4751 DOI: 10.1021/ja0213221
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66808
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:18 May 2016 00:39
Last Modified:26 Nov 2019 11:15

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