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  • Title: Enhanced biological activity of dimeric gonadotropin releasing hormone.
    Author: Kitajima Y, Catt KJ, Chen HC.
    Journal: Biochem Biophys Res Commun; 1989 Mar 31; 159(3):893-8. PubMed ID: 2539155.
    Abstract:
    The biological activities of a series of dimeric analogs of des-Gly10-[D-Lys6]GnRH-NHEt cross-linked at Lys6 by malonic acid and elongated by Gly, i.e., HO-Glyn-CO-CH2-CO-Glyn-OH (n = 0, 1, 2), were analyzed in vitro and in vivo. All three dimeric analogs displayed increased activity in receptor binding and in LH release assays than the original monomer, and dimer Ib (n = 1) showed the highest potency in vitro. This compound also showed the highest activity in the in vivo postcoital assay, in which GnRH agonist potency is measured by inhibition of pregnancy. These results indicate that GnRH receptor activation is substantially enhanced by dimerization of the agonist ligand.
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