Vo1.184, No. 3,1992 May 15,1992 BIOCHEMICAL AND BIOPHYSICAL RESEARCHCOMMUNICATIONS Pages 1273-]279 SERINE ANALOGUES OF hFSH-BETA-(33-53) AND hFSH-BETA-(81-95) INHIBIT hFSH BINDING TO RECEPTOR Tomas A. Santa-Coloma*, John W. Crabb I and Leo E. Reichert, Jr. Department of Biochemistry and Molecular Biology, Albany Medical College, Albany, New York 12208 1W.Alton Jones Cell Science Center, Lake Placid, NY 12948 Received March 9, 1992 Summary: Synthetic peptides corresponding to hFSH-beta-{33-53) and hFSH-beta-(81-95) each contain free sulfhydryl groups, inhibit binding of FSH to receptor and are partial agonists of estradiol synthesis in Sertoli cells. Recently, we have reported that sulfhydryl groups are important in FSH- receptor interaction and that peptides containing free sulfhydryl groups or disulfide bridges, such as glutathione, may nonspecifically inhibit FSH binding to receptor. In the present study, Cys residues of hFSH- beta-(33-53) and hFSH-beta-(81-95) were replaced by Ser residues and the peptides tested for their ability to inhibit binding of FSH to receptor. Results similar to those obtained previously with natural sequence peptides were obtained with the Ser analogs, indicating that Cys residues were not essential for binding inhibition. However, the partial agonist activity of the hFSH-beta-(33-53) and (81-95) in cultured Sertoli cells could not be detected when Cys residues were replaced by Ser. Thus, replacement of Cys residues with Ser does not effect receptor binding activity but is deleterious to the agonist activity of these peptides o © 1992 Academic Press, Inc. Follicle stimulating hormone (FSH) is a heterodimeric glycoprotein composed of two non-covalently associated subunits. Since the alpha-subunit of FSH is identical to the alpha-subunit of luteinizing hormone (LH), chorionic gonadotropin (CG) and thyrotropin (TSH), it is believed that hormone specificity resides in the beta subunit (1-4). Using a synthetic peptide approach, we have previously found that hFSH-beta subunit In Leave of absence from Consejo National de Investigaciones Cientificas y T~cnicas, Argentina. Present Address: National Institutes of Health, National Cancer Institute, Laboratory of Chemoprevention, Bethesda, MD 20892. 1273 0006-291X/92 $4.00 Copyright © 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.