Toward Artificial Developmental Regulators

Hans Dieter Arndt; Karl E. Hauschild; David P. Sullivan; Kara Lake; Peter B. Dervan; Aseem Z. Ansari

doi:10.1021/ja0371395

Toward Artificial Developmental Regulators

Hans Dieter Arndt, Karl E. Hauschild, David P. Sullivan, Kara Lake, Peter B. Dervan^*, Aseem Z. Ansari

^*Corresponding author for this work

Pathology

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Abstract

A polyamide?peptide conjugate is designed which recruits sequence specifically the developmental regulator Exd to a cognate DNA site. In particular, an eight-ring hairpin polyamide (Im-Im-Py(C₃H₆NHR)-Py-γ-Im-Py-Py-Py-β-Dp) with a heptapeptide (R = Ac-Phe-Tyr-Pro-Trp-Met-Lys-Gly-) attached on a central ring was shown to induce cooperative binding of the Drosophila Hox protein cofactor Exd with a K_d of 4.4 nM in vitro, an order of magnitude more efficient than the natural Hox protein partner Ubx. The conjugate joins two sequence specific domains, one for DNA and one for the protein. This small molecule thus serves as a cooperative protein?DNA dimerizer, which mimics the natural Hox family of developmental regulators.

Original language	English (US)
Pages (from-to)	13322-13323
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	125
Issue number	44
DOIs	https://doi.org/10.1021/ja0371395
State	Published - Nov 5 2003

ASJC Scopus subject areas

General Chemistry
Biochemistry
Catalysis
Colloid and Surface Chemistry

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AU - Arndt, Hans Dieter

AU - Hauschild, Karl E.

AU - Sullivan, David P.

AU - Lake, Kara

AU - Dervan, Peter B.

AU - Ansari, Aseem Z.

PY - 2003/11/5

Y1 - 2003/11/5

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Toward Artificial Developmental Regulators

Abstract

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