A novel and efficient method for synthetic carbohydrate conjugate vaccine preparation: Synthesis of sialyl Tn-KLH conjugate using a 4-(4-N-maleimidomethyl) cyclohexane-1-carboxyl hydrazide (MMCCH) linker arm Journal Article

  

Authors:	Ragupathi, G.; Koganty, R. R.; Qiu, D.; Lloyd, K. O.; Livingston, P. O.
Article Title:	A novel and efficient method for synthetic carbohydrate conjugate vaccine preparation: Synthesis of sialyl Tn-KLH conjugate using a 4-(4-N-maleimidomethyl) cyclohexane-1-carboxyl hydrazide (MMCCH) linker arm
Abstract:	STn (NeuAcα2 → 6GalNAcα-O-Ser/Thr) is a carbohydrate epitope overexpressed in various human carcinomas. Clinical trials are underway using synthetic STn or STn trimeric glycopeptides [STn, cluster; STn(c)l conjugated with keyhole limpet hemocyanin (KLH) as active specific immunotherapy for these cancers. These vaccines have been prepared by conjugating a crotyl ethyl amide derivative of STn or STn(c) to KLH by direct reductive amination after ozonolysis. In the case of STn(c) the conjugation efficiency and the resulting epitope ratios were low. This may be due to steric hinderance of the short spacer arm. To overcome these difficulties, without resynthesis, the STn(c) glycopeptide was modified by attachment of an MMCCH (4-(4-N-maleimidomethyl) cyclohexane-1-carboxyl hydrazide) spacer arm to the aldehyde derivative, and then conjugated with thiolated KLH. This method gave a higher epitope ratio and yield than the direct method. The STn(c)-MMCCH-KLH conjugate induced high titer antibodies in mice against STn(c). This method may be generally applicable for large synthetic oligosaccharides.
Keywords:	controlled study; unclassified drug; nonhuman; mouse; animals; mice; cancer immunotherapy; animal experiment; molecular sequence data; antigen; cancer vaccine; cancer vaccines; epitope; methods; technique; antigens, tumor-associated, carbohydrate; carbohydrate sequence; glycopeptide; antibody formation; antibody production; carbohydrate; vaccines; keyhole limpet hemocyanin; hemocyanin; vaccines, conjugate; immunization; maleimides; conjugation; epitopes; cross-linking reagents; conjugate; glycoconjugates; subcutaneous drug administration; cancer; humans; female; priority journal; article; aldehyde derivative; immunogen; 4 (4 n maleimidomethyl)cyclohexane 1 carboxylhydrazide
Journal Title:	Glycoconjugate Journal
Volume:	15
Issue:	3
ISSN:	0282-0080
Publisher:	Springer New York LLC
Date Published:	1998-03-01
Start Page:	217
End Page:	221
Language:	English
DOI:	10.1023/a:1006936826730
PUBMED:	9579798
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031887869&doi=10.1023%2fA%3a1006936826730&partnerID=40&md5=e46b20403e7824b4bf3ea0bf763052dc
Notes:	Article -- Export Date: 12 December 2016 -- Source: Scopus

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