2 research outputs found
Chemoenzymatically Prepared Heparan Sulfate Containing Rare 2āO-Sulfonated Glucuronic Acid Residues
The
structural diversity of natural sulfated glycosaminoglycans
(GAGs) presents major promise for discovery of chemical biology tools
or therapeutic agents. Yet, few GAGs have been identified so far to
exhibit this promise. We reasoned that a simple approach to identify
such GAGs is to explore sequences containing rare residues, for example,
2-O-sulfonated glucuronic acid (GlcA<i>p</i>2S). Genetic
algorithm-based computational docking and filtering suggested that
GlcA<i>p</i>2S containing heparan sulfate (HS) may exhibit
highly selective recognition of antithrombin, a key plasma clot regulator.
HS containing only GlcA<i>p</i>2S and 2-N-sulfonated glucosamine
residues, labeled as HS<sub>2S2S</sub>, was chemoenzymatically synthesized
in just two steps and was found to preferentially bind antithrombin
over heparin cofactor II, a closely related serpin. Likewise, HS<sub>2S2S</sub> directly inhibited thrombin but not factor Xa, a closely
related protease. The results show that a HS containing rare GlcA<i>p</i>2S residues exhibits the unusual property of selective
antithrombin activation and direct thrombin inhibition. More importantly,
HS<sub>2S2S</sub> is also the first molecule to activate antithrombin
nearly as well as the heparin pentasaccharide although being completely
devoid of the critical 3-<i>O</i>-sulfonate group. Thus,
this work shows that novel functions and mechanisms may be uncovered
by studying rare GAG residues/sequences
Gene trees and alignments for Musa gene orthogroups
These are the orthogroup gene trees and alignments that were used to phylogenetically place the polyploidy events suggested by the Musa acuminata genome. See the README files for a complete description