Hopping sugars: molecular mechanism of protonated glycans
rearrangement
Mateusz Marianski
Abstract
Carbohydrates, one of the three important classes of biopolymers, are involved in
a range of biological processes. Their multiple functions are facilitated by a high diver-
sity and adaptability of the glycan's molecular structure which, effectively, constitutes
a major challenge for glycoanalitic methods. The analysis by mass-spectroscopy
(MS) methods is often complicated by glycan rearrangements for which the molecu-
lar mechanism remains undetermined.
In order to analyze structural prerequisites and determine the molecular mech-
anism underpinning the rearrangement, I will design streamlined sampling protocol
that is able to screen both conformational (within one topology) and structural (be-
tween varying ion topologies) space. The density-functional theory methods are able
to link a glycan sequence and 3-dimensional structure of charged glycans, are able
to predict thermodynamically stable rearrangement products and propose tentative
molecular mechanism.
The sampling protocol will be next applied to set of oligosaccharides for which
glycan rearrangements, following different mechanism, has been observed. The gly-
cans include fucose migration in small Lewis A and Y antigens and their sialylated
forms, and larger biantennary N-glycan. Moreover, the structural space of these gly-
cans, including alternative epimers, will be explored to quantify structural prerequi-
sites governing the mechanism. The proposed tentative reaction mechanism will be
tested in tandem MS experiments with collaboration with Dr. Lin at Boston University
Medical School.
The proposal suggest a paradigm shift from explanatory to exploratory role of the-
oretical methods in describing the glycans. In effect, comprehensive understanding
of glycans structural space will shed lights on occurrence of multiple conformational
ensembles in ion-mobility spectrometry and will help to predict and red-¿ag erroneous
peaks in gas-phase based glycoanalysis.
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