CaltechAUTHORS
Published May 9, 2012 | Version Accepted Version + Supplemental Material
Journal Article Open

Pharmacokinetics of Py-Im Polyamides Depend on Architecture: Cyclic versus Linear

Creators

  • 1. ROR icon California Institute of Technology

Abstract

The pharmacokinetic properties of three pyrrole-imidazole (Py-Im) polyamides of similar size and Py-Im content but different shape were studied in the mouse. Remarkably, hairpin and cyclic oligomers programmed for the same DNA sequence 5′-WGGWWW-3′ displayed distinct pharmacokinetic properties. Furthermore, the hairpin 1 and cycle 2 exhibited vastly different animal toxicities. These data provide a foundation for design of DNA binding Py-Im polyamides to be tested in vivo.

Additional Information

© 2012 American Chemical Society. Received: March 16, 2012; Published: April 17, 2012. J.A.R. is grateful to the Alexander von Humboldt foundation for the award of a Feodor Lynen postdoctoral fellowship. A.E.H. thanks the California Tobacco-Related Disease Research Program (19FT-0105) and the NIH (NRSA number 1F32CA156833) for postdoctoral support. A.Y.S. acknowledges the NIH for postdoctoral funding (NRSA number 5F32CA139883). We are grateful for support by The Ellison Medical Foundation (AG-SS-2256-09) and the National Institutes of Health (GM051747). The authors declare no competing financial interest.

Attached Files

Accepted Version - nihms372939.pdf

Supplemental Material - ja302588v_si_001.pdf

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ja302588v_si_001.pdf

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Additional details

Identifiers

PMCID
PMC3349014
Eprint ID
31877
DOI
10.1021/ja302588v
Resolver ID
CaltechAUTHORS:20120611-162948738

Related works

Describes
10.1021/ja302588v (DOI)

Funding

Alexander von Humboldt Foundation
California Tobacco-Related Disease Research Program (TRDRP)
19FT-0105
NIH Postdoctoral Fellowship
1F32CA156833
NIH Postdoctoral Fellowship
5F32CA139883
Ellison Medical Foundation
AG-SS-2256-09
NIH
GM-051747

Dates

Created
2012-06-12
Created from EPrint's datestamp field
Updated
2021-11-09
Created from EPrint's last_modified field