Role of positive charge of lysine residue on ribosome-inactivating property of gelonin

Abstract

The report that gelonin cross-linked with monoclonal antibodies with the use of 2-iminothiolane (2-IT) exhibited higher cytotoxicity than the conjugates prepared with the use of N-succinimidyl-3-(2-pyridylthio) propionate (SPDP) alone, has prompted us to investigate the effect of ɛ-NH₂ group modification with 2-IT on the ribosome-inactivating property (RIP) of gelonin. The purified gelonin was modified with 2-IT at a different molar ratio and their effects on immunoreactivity and ribosome-

inactivating property were compared with those of N-succinimidyl 6-[3-(2-pyridyldithio) propionamido ] hexanoate (long chain-SPDP) and SPDP modified gelonin derivatives. Modification of single amino group with 2-IT results in about

<span style="font-size:12.0pt;font-family:" times="" new="" roman";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-in;mso-fareast-language:="" en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">25-50% inhibition of immunoreactivity and 60-70% loss of protein synthesis inhibition activity. Modification of 2-3 amino groups further hampers both immunoreactivity and protein synthesis inhibition property of gelonin. Both the long chain-SPDP with SPDP modifications showed more pronounced effects on immunoreactivity and RIP activity as compared to the similar ratio of 2-IT modification(s). It may, therefore, be concluded that the positive charge plays an important role in the immunological as well as the protein synthesis inhibitory effect of gelonin .</span>