title: Hormonotoxins. I. Strategy for synthesis of ovine luteinizing hormone--gelonin conjugate bearing the toxin in the beta-subunit.
abstract: The amino groups in the beta-subunit of ovine luteinizing hormone (oLH) were modified by thiolation using N-succinimidyl-3-(2-pyridyldithio) propionate so that it may be coupled in a disulfide linkage to similarly modified ribosome inactivating protein, gelonin. The modified beta-subunit was able to hybridize with free LH alpha-subunit and the complex retained full biological activity. However, when gelonin was coupled to the beta-subunit, the resulting conformational changes masked or eliminated the sites necessary for intersubunit recognition of the free alpha-subunit. This has important implications for the design in the synthesis of gonadotropin-toxin/drug conjugates.
authors.affiliation: Reproduction Research Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Singh
authors.forename: M R
authors.initials: MR
authors.lastname: Sairam
mesh_terms: D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D007986:Luteinizing Hormone / Q000138:chemical synthesis*; D010940:Plant Proteins / Q000138:chemical synthesis*; D011487:Protein Conformation; D054789:Ribosome Inactivating Proteins, Type 1; D012756:Sheep; D013388:Succinimides
chemical_list: D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D013388:Succinimides; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; C025674:GEL protein, Gelonium multiflorum; D007986:Luteinizing Hormone