Toward artificial developmental regulators.
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-gamma-Im-Py-Py-Py-beta-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 Kd 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.
California Institute of Technology, Division of Chemistry and Chemical Engineering, Pasadena, California 91125, USA.
Hans-Dieter
HD
Arndt
Karl E
KE
Hauschild
David P
DP
Sullivan
Kara
K
Lake
Peter B
PB
Dervan
Aseem Z
AZ
Ansari
D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D009757:Nylons / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009757:Nylons; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; C083405:exd protein, Drosophila; D004247:DNA