| Autor: |
Leng N; Albany Medical College, NY, USA., Grasso P, Reichert LE Jr |
| Jazyk: |
angličtina |
| Zdroj: |
Peptide research [Pept Res] 1996 Jul-Aug; Vol. 9 (4), pp. 188-94. |
| Abstrakt: |
We have used single- or double-point D-amino acid substitutions to study the structure-function relationships involving residues 32 to 46 of the glycoprotein hormone common alpha-subunit (GPHa) and the testicular follicle-stimulating hormone (FSH) and luteinizing hormone (LH/hCG) receptors. D-Amino acid substitution analogs of GPHa(32-46) were synthesized and tested in both FSH and hCG radioligand receptor assays using bovine calf testis membranes as receptor source. Correct orientation of the amino acid side chains was generally of paramount importance for peptide interaction with receptor and bioactivity. Most substitutions with corresponding D-amino acids did not enhance the potency of native GPHa(32-46). A significant increment in peptide potency, however, was observed by inversion of configuration at positions Ser-34 and Thr-39 with D-amino acid isoforms. Based on the relative potency of each peptide analog. [D-Ser-34, D-Thr-39]GPHa(32-46) was approximately twofold more potent than native peptide GPHa(32-46) in both FSH and hCG radioligand receptor assays. [D-Ser-34, D-Thr-39]GPHa(32-46) also markedly inhibited FSH-stimulated estradiol biosynthesis in cultured rat Sertoli cells. The present study is unique in that it represents the first report of utilizing D-amino acid substitution to develop more potent peptide analogs related to the glycoprotein hormone common alpha-subunit region 32-46. Our results offer hope for the development of more potent and stabile peptide antagonists of possible usefulness in fertility regulation and control. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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