Design of novel antiestrogens

Lawrence B. Hendry, Chung K. Chu, Mary L. Rosser, John A. Copland, Joseph C. Wood, Virendra B. Mahesh

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The physicochemical principle of "die and coin" complementarity proffered by Pauling and Delbruck and exemplified in Watson and Crick DNA was used to design new antineoplastic compounds. In search of an explanation for why certain molecules and not others are present in nature, biologically active small molecules were discovered to exhibit complementarity when inserted into cavities between base pairs in DNA. Ligands in the steroid/thyroid hormone/vitamin D family fit particularly well into the site 5′-dTdG-3′·5′dCdA-3′. Degree of fit of various candidate compounds in the manner of a given hormone correlated with degree of hormonal activity. Hormone antagonists fit into the same site but in a different manner than the agonists. Computer graphics and energy calculations confirmed salient observations including the remarkable complementarity of estradiol and DNA. Using the above criteria, a new candidate antiestrogen, para-hydroxyphenyl-acetylamino-2,6-piperidinedione was successfully designed. Taken as a whole, these results coupled with recent independent findings raise the possibility that the mode of action of certain hormones and hormone antagonists may involve direct insertion into DNA mediated by classical protein receptors and other transcription factors.

Original languageEnglish (US)
Pages (from-to)269-280
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume49
Issue number4-6
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Estrogen Receptor Modulators
Hormone Antagonists
DNA
Hormones
Computer Graphics
Numismatics
Molecules
Computer graphics
Thyroid Hormones
Vitamin D
Base Pairing
Antineoplastic Agents
Estradiol
Transcription Factors
Steroids
Ligands
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Hendry, L. B., Chu, C. K., Rosser, M. L., Copland, J. A., Wood, J. C., & Mahesh, V. B. (1994). Design of novel antiestrogens. Journal of Steroid Biochemistry and Molecular Biology, 49(4-6), 269-280. https://doi.org/10.1016/0960-0760(94)90268-2

Design of novel antiestrogens. / Hendry, Lawrence B.; Chu, Chung K.; Rosser, Mary L.; Copland, John A.; Wood, Joseph C.; Mahesh, Virendra B.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 49, No. 4-6, 1994, p. 269-280.

Research output: Contribution to journalArticle

Hendry, LB, Chu, CK, Rosser, ML, Copland, JA, Wood, JC & Mahesh, VB 1994, 'Design of novel antiestrogens', Journal of Steroid Biochemistry and Molecular Biology, vol. 49, no. 4-6, pp. 269-280. https://doi.org/10.1016/0960-0760(94)90268-2
Hendry LB, Chu CK, Rosser ML, Copland JA, Wood JC, Mahesh VB. Design of novel antiestrogens. Journal of Steroid Biochemistry and Molecular Biology. 1994;49(4-6):269-280. https://doi.org/10.1016/0960-0760(94)90268-2
Hendry, Lawrence B. ; Chu, Chung K. ; Rosser, Mary L. ; Copland, John A. ; Wood, Joseph C. ; Mahesh, Virendra B. / Design of novel antiestrogens. In: Journal of Steroid Biochemistry and Molecular Biology. 1994 ; Vol. 49, No. 4-6. pp. 269-280.
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