Target-directed enediynes: designed estramycins.

The goal of selective targeting of enediyne cytotoxins has been investigated using estrogenic delivery vehicles. A series of estrogen-enediyne conjugates were assembled, and affinity for human estrogen receptor [hERalpha] was determined. The most promising candidate induced receptor degradation following Bergman cycloaromatization and caused inhibition of estrogen-induced transcription in T47-D human breast cancer cells.

Protein-degrading enediynes: library screening of Bergman cycloaromatization products.

[structure: see text] A screening method based on Bergman cycloaromatization products was applied to a compact library of estrogenic-enediyne hybrids. An enediyne candidate identified from the screen was subsequently synthesized, and it induced temperature- and concentration-dependent degradation of human estrogen receptor alpha upon cycloaromatization.

Functional analysis of a novel estrogen receptor-beta isoform.

A new level of complexity has recently been added to estrogen signaling with the identification of a second estrogen receptor, ERbeta. By screening a rat prostate cDNA library, we detected ERbeta as well as a novel isoform that we termed ERbeta2. ERbeta2 contains an in-frame inserted exon of 54 nucleotides that results in the predicted insertion of 18 amino acids within the ERbeta hormone-binding domain.

Translational and pretranslational regulation of protein synthesis by amino acid availability in primary cultures of rat hepatocytes.

Protein synthesis is inhibited in both rat liver and isolated rat hepatocytes following deprivation of single essential amino acids. The aim of the present study was to define the time course of changes in peptide-chain initiation, albumin synthesis, and albumin mRNA following histidine deprivation and the reversal of these changes in response to readdition of the deprived amino acid. A further aim was to ascertain whether there was an accommodation of the inhibition of initiation following long-term amino acid deprivation.