Computational design, synthesis, and evaluation of miniproteins as androgen receptor coactivator mimics

Chem Commun (Camb). 2009 Sep 28:(36):5377-9. doi: 10.1039/b910677d. Epub 2009 Aug 17.

Abstract

Insertion of 3 to 4 mutations, based on in silico modelling, in a diverse set of natural miniproteins generates potent androgen receptor (AR) binders and a clear insight into the structure-activity relationship of such coactivator mimics concerning helix length.

MeSH terms

  • Amino Acid Sequence / genetics
  • Androgens*
  • Apamin / chemistry
  • Apamin / genetics
  • Binding, Competitive
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Databases, Protein
  • Drug Design*
  • Humans
  • Models, Molecular
  • Molecular Mimicry
  • Molecular Sequence Data
  • Mutation / genetics
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs / genetics
  • Protein Structure, Secondary
  • Receptors, Androgen / metabolism*
  • Scorpion Venoms / chemistry
  • Scorpion Venoms / genetics
  • Structure-Activity Relationship
  • Toxins, Biological / chemistry
  • Toxins, Biological / genetics
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Androgens
  • DNA-Binding Proteins
  • Peptides
  • Receptors, Androgen
  • Scorpion Venoms
  • Toxins, Biological
  • Transcription Factors
  • leiurotoxin I
  • TMF1 protein, human
  • Apamin