{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T17:03:10Z","timestamp":1698944590051},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,10,4]],"date-time":"2004-10-04T00:00:00Z","timestamp":1096848000000},"content-version":"vor","delay-in-days":277,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopolymers"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Currently used antiestrogenic drugs against hormone\u2010dependent breast cancer, and estrogenic drugs used in treatment of osteoporosis, are associated with risk factors. Therefore, there is a strong need to develop selective estrogen receptor modulators with better tissue selectivity. In a recent study (Peptides, 2002, Vol. 3, 573\u2013580), we used a monoclonal antibody to estradiol (mAb\u2010E2) to screen a phage\u2010display peptide library. We identified a 15\u2010mer peptide (peptide H5) that recognizes mAb\u2010E2 (IC<jats:sub>50<\/jats:sub> 1 \u03bcM) and estrogen receptor (ER)\u03b1 (IC<jats:sub>50<\/jats:sub> 500 \u03bcM) but not ER\u03b2, and displays estrogen\u2010like activity in vitro and in vivo. In this study, we designed and prepared peptides based on peptide H5, which possess improved estrogenic activity, by evaluating their binding to mAb\u2010E2 and to ERs. Initially, we determined the minimal binding sequence of peptide H5 capable of binding mAb\u2010E2 and ER. Subsequently, systematic single\u2010residue replacements of the minimal sequence, followed by multiple\u2010residue replacements, yielded hexa\u2010 and heptapeptides with increased affinities to mAb\u2010E2 and to ER. The most promising peptides, VSWFFE (EMP\u20101) and VSWFFED (EMP\u20102) (EMP: estrogen\u2010mimetic peptide), bind mAb\u2010E2 with high affinity (IC<jats:sub>50<\/jats:sub> of 6 and 30 nM, respectively), recognize ERs with increased affinity (IC<jats:sub>50<\/jats:sub> of 100 \u03bcM for ER\u03b1, and 100\u2013250 \u03bcM for ER\u03b2), and possess estrogenic activity in vivo. The short peptides described in this study may be used as potential lead compounds for developing new ER ligands. \u00a9 2004 Wiley Periodicals, Inc. 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