Synthesis of complex oligosaccharides and glycoconjugates: chemoselectivity and orthogonality of modern building blocks.
Development of expeditious strategies for oligosaccharide synthesis
There is no universal method for the synthesis of glycans whether manual or automated. Regardless of the approach, building blocks are made manually. Then a strategic planning of protecting and leaving groups is required.
Pros: many strategies are available
Cons: can be lengthy and inefficient, requires specialized training
Pros: complete automation minimizes operator
intervention and improves reproducibility
Cons: glycosylations can be incomplete, harder to control, large excess of building blocks is needed, most equipment and resins are designed for peptides
Glycoworld's Contribution to Glycan Assembly
Glycosylation represents only one challenge oligosaccharide synthesis researchers face; often additional protecting or leaving group manipulations between each glycosylation step are required. This becomes increasingly inefficient at advanced stages of the assembly, often leading to a dramatic drop in yield, and, consequently, a decrease in the availability of oligosaccharides.
To address these challenges, Glycoworld introduced the following strategies for expeditious oligosaccharide synthesis: the temporary deactivation concept, the inverse armed-disarmed strategy, electronically superarmed and superdisarmed building blocks, templated oligosaccharide synthesis, and the reverse orthogonal strategy. The group at Glycoworld also developed five new sets of leaving groups for orthogonal activation.
Visansirikul, S. A. Kolodziej, and A. V. Demchenko. Synthesis of oligosaccharide fragments of capsular polysaccharide Staphylococcus aureus type 8. Carbohydr. Chem., 2020, 39, 301-333
D. Bandara, K. J. Stine, and A. V. Demchenko. Chemical synthesis of human milk oligosaccharides: lacto-N-neohexaose [Galβ1®4GlcNAcβ1®]2 3,6-Galβ1®4Glc. Org. Biomol. Chem., 2020, 18, 1747-1753 (Front Cover)
PMID: 32048706 (2R01-3, U01-23)
D. Bandara, K. J. Stine, and A. V. Demchenko. Chemical synthesis of human milk oligosaccharides: lacto-N-hexaose Galβ1 → 3GlcNAcβ1 → 3[Galβ1 → 4GlcNAcβ1 → 6]Galβ1 → 4Glc. J. Org. Chem., 2019, 84, 16192-16198
PMID: 31749363 (1R01-29, U01-20)
New technologies for the automated glycan assembly
More recently, my lab has been working on automated technologies for oligosaccharide synthesis: STICS (Surface-Tethered Iterative Carbohydrate Synthesis) and HPLC-assisted automated synthesis (HPLC-A) in collaboration with Keith Stine, a biophysical surface chemist at the University of Missouri – St. Louis.
The general idea for developing the HPLC-A is that a computer interface coupled with standard HPLC components will allow recording a successful automated sequence as a computer program that can then be reproduced with the “press of a button.” The application of this user-friendly platform for simple and transformative automation to produce glycans is currently being investigated with involvement of undergraduate and high school students.
HPLC-A is now based on a completely automated and a user-friendly, windows-like platform
M. Panza, D. Neupane, K. J. Stine, and A. V. Demchenko. The development of a dedicated polymer support for the solid-phase oligosaccharide synthesis. Chem. Commun., 2020, 56, 10568-10571
PMID: 32785304 (2R01-9, U01-25)
M. Panza, K. J. Stine, and A. V. Demchenko. HPLC-assisted automated oligosaccharide synthesis: the implementation of the two-way split valve as a mode of complete automation. Chem. Commun., 2020, 56, 1333-1336 (Inside Back Cover)
PMID: 31930269 (2R01-2, U01-22)
Panza, S. G. Pistorio, K. J. Stine, A. V. Demchenko. Automated chemical oligosaccharide synthesis: novel approach to traditional challenges. Chem. Rev., 2018, 118, 8105-8150
PMID: 29953217 (1R01-25, U01-6)
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