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Synthesis and Conformational Analysis of the T‐Antigen Disaccharide (β‐ D ‐Gal‐(1→3)‐α‐ D ‐GalNAc‐OMe)
Author(s) -
Bukowski Ralph,
Morris Laura M.,
Woods Robert J.,
Weimar Thomas
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200107)2001:14<2697::aid-ejoc2697>3.0.co;2-0
Subject(s) - disaccharide , chemistry , monte carlo method , glycosyl , stereochemistry , population , computational chemistry , molecular dynamics , crystallography , statistics , demography , mathematics , sociology
We report an improved synthesis of the T‐antigen disaccharide [β‐ D ‐Gal‐(1→3)‐α‐ D ‐GalNAc‐OMe], incorporating recycling of the undesired β‐glycosyl acceptor [methyl 2‐azido‐4,6‐benzylidene‐2‐deoxy‐β‐ D ‐galactopyranoside ( 9β )] through anomerization by treatment with FeCl 3 . The conformational analysis of the disaccharide made use of high quality NOE data in combination with extensive Metropolis Monte‐Carlo (MMC) and molecular dynamic (MD) simulations. To sample the conformational space sufficiently, 9.5·10 6 Monte‐Carlo steps were collected for the MMC simulations, while the fully solvated MD simulations were performed for 10 ns for comparison. In general, the MMC and MD simulations agreed very well. Comparison of theoretical NOE curves from both MMC and MD simulations with the experimental curves showed that the disaccharide populates two regions of conformational space, with a population of about 95% for the global minimum energy region and about 5% for a local minimum energy region.