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Medchem & Toxicology 2018
Page 48
Journal of Organic & Inorganic Chemistry
ISSN: 2472-1123
A n n u a l C o n g r e s s o n
Medicinal Chemistry,
Pharmacology and toxicology
J u l y 3 0 - 3 1 , 2 0 1 8
Am s t e r d a m , N e t h e r l a n d s
Cancer-associated mucin glycoprotein MUC1 is characterized by the
presence of altered carbohydrates such as Tn (-N-acetylgalactosamine),
sTn (sialyl-1-6-Tn) and the Thomsen-Friedenreich (TF: -D-Galp-1-3-D-
GalNAcp) antigen (tumor associated carbohydrate antigens: TACAs) that
are conjugated to proteins via O--galactosylation of serine or/and threonine.
Patients immunized with synthetic TF conjugated with KLH (keyhole limpet
hemocyanin) + QS21 adjuvant can generate IgM and IgG antibodies.1 Because
the disaccharide TF is hydrolyzed rapidly in the body, strong immune response
requires longer lived disaccharides. Fluororinated TACAs have been proposed
which elicit IgG antibodies found to cross-react with native TF epitopes.2,3 We
have found that the C-linked disaccharide analogue 1 (constructed applying
Danishesky's method for the conjugation with KLH 4) + QS21 adjuvant induces
a strong immune response in mice. Interestingly, much weaker immune
response was observed with a stereoisomeric antigen constructed with the
-C-galactoside analogue of TF disaccharide (-D-Galp-1-CH2-3--D-GalNAc-O-
Ser).5 Several strategies and methods have been developed for the synthesis
of C-linked disaccharides including disaccharide mimetics incorporating
iminosugars C-linked to sugars and sugar mimetics such as conduritols and
cyclitols. The latter work was motivated by the search for specific glycosidase
and glycosyltransferase inhibitors that are potential drugs against cancers and
other diseases.
Biography
P. Vogel was born in Cully (Switzerland) Oct. 23, 1944. In 1969,
he did his Ph.D under supervision of Prof. H. Prinzbach at the
Institute of Organic Chemistry, University of Lausanne. He spent
two years at Yale University, New Haven, Connecticut, USA with
Prof. Martin Saunders, Prof. J. A. Berson, K. A. Wiberg and P.v.R.
Schleyer (Princeton Universtiy). He worked then as a Research
chemist at Syntex S.A., in Mexico with Prof. P.Crabbé before
the return to the University of Lausanne in 1973. As of 1977
he became Professor of organic chemistry at the University
of Lausanne. In 1991 he was Vice-Chairman of the Institute of
organic Chemistry, University of Lausanne until 2001. He was
also part-time grad.school teacher at the Universities of Rouen
and Caen from 1991 to 1993 and Part-time professor at Ecole
Polytechnique de Palaiseau from 1993-2000. Since 2001 he is
Professor of organic chemistry at the EPFL.
Sugar mimetics toward an anti-cancer therapeutic vaccine
Pierre Vogel and Loay Awad
Swiss Institute of Technology in Lausanne (EPFL), CH 1015 Lausanne, Switzerland
Pierre Vogel et al., J Org Inorg Chem 2018, Volume 4
DOI: 10.21767/2472-1123-C3-008
O O
HO OH HO
OH
NH OH
HO
O
H
H Ac
CO- HN NH-spacer R
3 1 KLH
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