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dc.contributor.authorAlam, Anis-
dc.contributor.authorSingh, Ranjit C-
dc.contributor.authorSingh, Vinod-
dc.identifier.issn0975-1009 (Online); 0019-5189 (Print)-
dc.description.abstractWith the aim of developing a cytotoxic agent that could selectively target the appropriate steroid producing cells in the gonads, hormone-toxin conjugates were synthesized with the use of different heterobifunctional cross linking agents (HBCLA) such as, 2-iminothiolane HCl (2IT), N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP, 8.6 A) and Nsuccinimidyl 6-[3-(2-pyridyldithio) propionamido] hexanoate (LC-SPDP, 15.6 A). A complete physico-chemical, immunochemical and biochemical analysis was performed. The linkage occurred through the -NH2 groups of α-subunit of oLH as analysed by RP-HPLC analysis. But it was difficult to ascertain the site of linkage in hCG-gelonin conjugate. A 1:1 (hormone:gelonin) molar ratio was obtained when determined with spectrophotometric, gel electrophoresis and amino acid composition methods. The competitive displacement analysis indicates that the binding occurs via the hormone part and leaving gelonin free which was probed with the gelonin antibodies. The conjugates exhibited comparable immunoreactivity but the receptor binding and cytotoxicity of the conjugates prepared with 2IT were higher than the hormonotoxin prepared with the use of SPDP or LC-SPDP. Therefore, it is concluded that higher receptor binding and cytotoxicity may be due to the retention of positive charge on the lysine residues of oLH, which was preserved during the conjugation process. However, the cytotoxicity of oLH based hormonotoxins remained unaffected with the use of long chain spacer arm that is believed to be used generally to avoid steric hindrance. Based on the data presented here, it may be concluded that it is possible to synthesize oLH or hCG based hormonotoxins which specifically interacted with LH/hCG receptor and significantly inhibited protein synthesis in the tumor cells bearing receptors for gonadotropins. The detailed in vivo experiments under investigation would further demonstrate their effectiveness. If successful, a new class of luteolytic may be available in future. en_US
dc.publisherNISCAIR-CSIR, Indiaen_US
dc.rights CC Attribution-Noncommercial-No Derivative Works 2.5 Indiaen_US
dc.sourceIJEB Vol.40(04) [April 2002]en_US
dc.titleDesign and synthesis of hormonotoxin for selective targeting of gonadal cellsen_US
Appears in Collections:IJEB Vol.40(04) [April 2002]

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