Steroid structural requirements for high affinity binding to human sex steroid binding protein (SBP)

G. R. Cunningham, D. J. Tindall, T. J. Lobl, J. A. Campbell, A. R. Means

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The sex steroid binding protein (SBP) which binds androgens circulating in the blood of man has been examined to determine the structural requirements for high affinity binding. SBP was purified partially and the ability of each of more than 150 steroids to compete with [3H]dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) for binding to SBP was assessed. Binding was enhanced by reduction of the Δ4 double bond to 5α-dihydro, addition of a methyl group at C-4 and in one case unsaturation at C-14, 15. Affinity was always reduced by modifications of the C-17β hydroxy. Binding was also severely decreased by deletion of the keto moiety at C-3; however, relatively high affinity was retained by an alcohol or an unsubstituted pyrazole group at C-3. Certain alpha surface substitutions such as 17α-ethinyl had limited effects on binding; whereas, other modifications such as 7α-methyl or 17α-methyl caused significant reduction in binding. Most modifications at C-2, 6, 9 or 11 also impaired affinity, and the 5β steroids had reduced affinity.

Original languageEnglish (US)
Pages (from-to)243-262
Number of pages20
JournalSteroids
Volume38
Issue number3
DOIs
StatePublished - Sep 1981

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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