Serine analogues of hFSH-beta-(33-53) and hFSH-beta-(81-95) inhibit hFSH binding to receptor.
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.
Santa-Coloma
T A
TA
Department of Biochemistry and Molecular Biology, Albany Medical College, New York 12208.
Crabb
J W
JW
Reichert
L E
LE
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D037201:Follicle Stimulating Hormone, beta Subunit / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D011962:Receptors, FSH / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013737:Testis / Q000378:metabolism
C074634:FSH-beta-(33-53), human, Ser(51)-; C074635:FSH-beta-(81-95), human, Ser(82,84,87,94)-; D037201:Follicle Stimulating Hormone, beta Subunit; D010446:Peptide Fragments; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone