Solution structure of a synthetic peptide corresponding to a receptor binding region of FSH (hFSH-β 33–53)

Abstract

The receptor binding surface of human follicle-stimulating hormone (hFSH) is mimicked by synthetic peptides corresponding to the hFSH-beta chain amino acid sequences 33-53 [Santa-Coloma, T. A., Dattatreyamurty, D., and Reichert, L. E., Jr. (1990), Biochemistry 29, 1194-1200], 81-95 [Santa-Coloma, T. A., Reichert, L. E., Jr. (1990), J. Biol. Chem. 265, 5037-5042], and the combined sequence (33-53)-(81-95) [Santa-Coloma, T. A., Crabb, J. W., and Reichert, L. E., Jr. (1991), Mol. Cell. Endocrinol. 78, 197-204]. These peptides have been shown to inhibit binding of hFSH to its receptor. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy were used to determine the structure of the first peptide in this series, the 21 amino acid peptide hFSH-beta-(33-53), H2N-YTRDLVYKDPARPKIQKTCTF-COOH. Analysis of CD data indicated the presence of approximately equal amounts of antiparallel beta-pleated sheet, turns including a beta-turn, "other" structures, and a small amount of alpha-helix. The major characteristics of the structure were found to be relatively stable at acidic pH and the predominant effect of increased solvent polarity was a small increase in alpha-helical content. One- and two-dimensional NMR techniques were used to obtain full proton and carbon signal assignments in aqueous solution at pH 3.1. Analysis of NMR results confirmed the presence of the structural features revealed by CD analysis and provided a detailed picture of the secondary structural elements and global folding pattern in hFSH-beta-(33-53). These features included an antiparallel beta-sheet (residues 38-51 and 46-48), turns within residues 41-46, and 50-52 (a beta-turn) and a small N-terminal helical region comprised of amino acids 34-36. One of the turns is facilitated by prolines 42 and 45. Proline-45 was constrained to the trans conformation, whereas proline-42 favored the trans conformer (approximately 70%) over the cis (approximately 30%). Two resonances were observed for the single alanine residue (A-43) sequentially proximal to P-42, but the rest of the structure was minimally affected by the isomerization at proline-42. The major population of molecules, containing trans-42 and trans-45 prolines, presented 120 NOEs. Distance geometry calculations with 140 distance constraints and energy minimization refinements were used to derive a moderately well-defined model of the peptide's structure.(ABSTRACT TRUNCATED AT 400 WORDS)

Follicle-Stimulating Hormone Peptide Can Facilitate Paclitaxel Nanoparticles to Target Ovarian Carcinoma In vivo

“…Because FSH h 33-53 has the strongest binding affinity (data not shown; ref. 24), it is used in our system as a target-specific ligand to distribute drugs to ovarian tumor tissue.…”

“…This expression pattern makes it possible to use FSHR as the target site against ovarian cancer. FSH is a glycoprotein hormone consisting of a and h chains, and some FSHR-binding domains have been identified, including amino acids 1 to 15, 33 to 53, 51 to 65, and 81 to 95 of the FSH h chain (23)(24)(25)(26). Because FSH h 33-53 has the strongest binding affinity (data not shown; ref.…”

An investigation on the anti-tumor properties of FSH33-53-Lytic

“…FSH peptide has high affinity to FSHR [22,23]. Xu, et al [24,25], prepared new positron emission tomography (PET) probes such as 18 F-Al-NOTA-MAL-FSH 33-53 and 68 Ga-Al-NOTA-MAL-FSH , then evaluated the imaging performance in PC3 human prostate tumor xenograft by microPET image.…”

Analysis of glycoprotein hormone receptor extracellular domain interactions using a solid-phase capture assay

“…The importance of this receptor in maintaining fertility [4] has made it an attractive target for the development of speciWc agonists and antagonists that could be used to modulate hFSHR function [5,6]. There have been several reports describing peptidic ligands, derived from the FSH or FSHR primary sequence, that modulate FSH binding [3,[7][8][9][10][11]. It is well established that the primary contact sites for FSH interaction with its receptor are mediated by the ECD [12,13].…”