A synthetic peptide with estrogen-like activity derived from a phage-display peptide library.
We describe a novel approach to develop peptides with estrogen like activity using a monoclonal antibody specific to estradiol (mAb E2-15) for the affinity selection of phage displayed peptides from a combinatorial peptide library. Based on the sequences of the selected phage, we synthesized a 15-mer linear peptide LPALDPTKRWFFETK which was derivatized to a 23 mer cyclic peptide CAELPALDPTKRWFFETKPPPPC. Both peptides displayed estrogen-like activity according to the following criteria:(i) in inhibiting the binding of [3H]estradiol to mAb E2-15 and to estrogen receptor (ER)alpha; (ii) in inducing transcriptional activity in MCF7 human breast cancer cells transfected with an estrogen receptor element luciferase construct and (iii) in causing an increase in creatine kinase specific activity in rat tissues in vivo. This approach can be employed to design peptide mimetic for other hormones as well.
Venkatesh
Natarajan
N
Departments of Biological Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel.
Zaltsman
Yehudith
Y
Somjen
Dalia
D
Gayer
Batya
B
Boopathi
Ettickan
E
Kasher
Roni
R
Kulik
Tikva
T
Katchalski-Katzir
Ephraim
E
Kohen
Fortune
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003402:Creatine Kinase / Q000378:metabolism; D004958:Estradiol / Q000276:immunology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000276:immunology; D020849:Raloxifene Hydrochloride / Q000037:antagonists & inhibitors; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014316:Tritium; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D019151:Peptide Library; D010455:Peptides; D010456:Peptides, Cyclic; D011960:Receptors, Estrogen; D014316:Tritium; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D003402:Creatine Kinase