Ribosome-inactivating property of gelonin is more affected by N-succinimidyl 6-[3-(2-pyridyldithio) propionamido]hexanoate modification than N-succinimidyl-3- (2-pyridylthio) propionate

Abstract

As gelonin cross-linked to carrier proteins has been found as an effective hybrid complex for selective targeting to specific <span style="font-size:14.0pt;font-family:HiddenHorzOCR;mso-bidi-font-family:HiddenHorzOCR">cells, the ε-NH₂ group of gelonin(s) obtained by different methods has been sequentially modified by N-succinimidyl 6-[3-(2-pyridyldithio) propionamido] hexanoate (long chain-SPDP) and its effect on immunoreactivity and ribosome inactivating

<span style="font-size:14.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">property has been compared with that of N-succinimidyl-3-(2-pyridylthio) propionate (SPDP) modified gelonin. Modification of single amino group results in about 80% inhibition of immunoreactivity and more than 90% loss of protein synthesis-inhibition activity. Modification of 2-3 amino groups further hampers both immunoreactivity and protein synthesis inhibition property of gelonin. Upon comparison of long chain-SPDP with SPDP modification, the long chain-SPDP modification plays more pronounced effect on immunoreactivity and ribosome-inactivating property (RIP) activity than that of SPDP. It may, therefore, be concluded that the increase in carbon-chain spacer arm, although may provide less steric hindrance for receptor recognition of the carrier protein, has inhibitory effect on the cytotoxic activity of <span style="font-size:14.0pt;font-family:HiddenHorzOCR;mso-hansi-font-family:" times="" new="" roman";="" mso-bidi-font-family:hiddenhorzocr;mso-ansi-language:en-us;mso-fareast-language:="" en-us;mso-bidi-language:ar-sa"="">gelonin .</span></span></span>