Sequences in the HSP90 promoter form G-quadruplex structures with selectivity for disubstituted phenyl bis-oxazole derivatives

Stephan A. Ohnmacht; Marialuisa Micco; Vanessa Petrucci; Alan K. Todd; Anthony P. Reszka; Mekala Gunaratnam; Marta A. Carvalho; Mire Zloh; Stephen Neidle

doi:10.1016/j.bmcl.2012.07.065

Sequences in the HSP90 promoter form G-quadruplex structures with selectivity for disubstituted phenyl bis-oxazole derivatives

Stephan A. Ohnmacht, Marialuisa Micco, Vanessa Petrucci, Alan K. Todd, Anthony P. Reszka, Mekala Gunaratnam, Marta A. Carvalho, Mire Zloh, Stephen Neidle

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

The HSP90 protein is an important target in cancer. We report here that stable quadruplex DNAs can be formed from a promoter sequence in the HSP90 gene, on the basis of melting, circular and NMR studies, and show that these can be selectively targeted by non-macrocyclic quadruplex-stabilizing phenyl bis-oxazole derivatives. These do not bind significantly to duplex DNA and show low stabilization of the human telomeric quadruplex. These results suggest an approach to targeting HSP90 at the DNA level.

Original language	English
Pages (from-to)	5930-5
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2012.07.065
Publication status	Published - 2012

Access to Document

10.1016/j.bmcl.2012.07.065

Cite this

@article{18eef2e5d4a243a3b3b3bcf42c1199cc,

title = "Sequences in the HSP90 promoter form G-quadruplex structures with selectivity for disubstituted phenyl bis-oxazole derivatives",

abstract = "The HSP90 protein is an important target in cancer. We report here that stable quadruplex DNAs can be formed from a promoter sequence in the HSP90 gene, on the basis of melting, circular and NMR studies, and show that these can be selectively targeted by non-macrocyclic quadruplex-stabilizing phenyl bis-oxazole derivatives. These do not bind significantly to duplex DNA and show low stabilization of the human telomeric quadruplex. These results suggest an approach to targeting HSP90 at the DNA level.",

author = "Ohnmacht, {Stephan A.} and Marialuisa Micco and Vanessa Petrucci and Todd, {Alan K.} and Reszka, {Anthony P.} and Mekala Gunaratnam and Carvalho, {Marta A.} and Mire Zloh and Stephen Neidle",

year = "2012",

doi = "10.1016/j.bmcl.2012.07.065",

language = "English",

volume = "22",

pages = "5930--5",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

number = "18",

}

TY - JOUR

T1 - Sequences in the HSP90 promoter form G-quadruplex structures with selectivity for disubstituted phenyl bis-oxazole derivatives

AU - Ohnmacht, Stephan A.

AU - Micco, Marialuisa

AU - Petrucci, Vanessa

AU - Todd, Alan K.

AU - Reszka, Anthony P.

AU - Gunaratnam, Mekala

AU - Carvalho, Marta A.

AU - Zloh, Mire

AU - Neidle, Stephen

PY - 2012

Y1 - 2012

N2 - The HSP90 protein is an important target in cancer. We report here that stable quadruplex DNAs can be formed from a promoter sequence in the HSP90 gene, on the basis of melting, circular and NMR studies, and show that these can be selectively targeted by non-macrocyclic quadruplex-stabilizing phenyl bis-oxazole derivatives. These do not bind significantly to duplex DNA and show low stabilization of the human telomeric quadruplex. These results suggest an approach to targeting HSP90 at the DNA level.

AB - The HSP90 protein is an important target in cancer. We report here that stable quadruplex DNAs can be formed from a promoter sequence in the HSP90 gene, on the basis of melting, circular and NMR studies, and show that these can be selectively targeted by non-macrocyclic quadruplex-stabilizing phenyl bis-oxazole derivatives. These do not bind significantly to duplex DNA and show low stabilization of the human telomeric quadruplex. These results suggest an approach to targeting HSP90 at the DNA level.

U2 - 10.1016/j.bmcl.2012.07.065

DO - 10.1016/j.bmcl.2012.07.065

M3 - Article

C2 - 22892119

SN - 0960-894X

VL - 22

SP - 5930

EP - 5935

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 18

ER -

Sequences in the HSP90 promoter form G-quadruplex structures with selectivity for disubstituted phenyl bis-oxazole derivatives

Abstract

Access to Document

Fingerprint

Cite this