Computational design, synthesis, and evaluation of miniproteins as androgen receptor coactivator mimics.
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.
Vaz
Belen
B
Chemical Genomics Centre of the Max Planck Society, Otto-Hahn Strasse 15, 44227 Dortmund, Germany.
Möcklinghoff
Sabine
S
Folkertsma
Simon
S
Lusher
Scott
S
de Vlieg
Jacob
J
Brunsveld
Luc
L
D000595:Amino Acid Sequence / Q000235:genetics; D000728:Androgens; D001030:Apamin / Q000737:chemistry / Q000235:genetics; D001667:Binding, Competitive; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D030562:Databases, Protein; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D017433:Protein Structure, Secondary; D011944:Receptors, Androgen / Q000378:metabolism*; D012604:Scorpion Venoms / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D000728:Androgens; D004268:DNA-Binding Proteins; D010455:Peptides; D011944:Receptors, Androgen; D012604:Scorpion Venoms; D014118:Toxins, Biological; D014157:Transcription Factors; C056574:leiurotoxin I; C077335:TMF1 protein, human; D001030:Apamin