Synthesis and Binding of Mannose-Specific Synthetic Carbohydrate Receptors.
Chemistry
; 26(51): 11782-11795, 2020 Sep 10.
Article
in English
| MEDLINE | ID: covidwho-777429
ABSTRACT
Synthetic carbohydrate receptors (SCRs) that selectively recognize cell-surface glycans could be used for detection, drug delivery, or as therapeutics. Here we report the synthesis of seven new C2h symmetric tetrapodal SCRs. The structures of these SCRs possess a conserved biaryl core, and they vary in the four heterocyclic binding groups that are linked to the biaryl core via secondary amines. Supramolecular association between these SCRs and five biologically relevant C1 -O-octyloxy glycans, α/ß-glucoside (α/ß-Glc), α/ß-mannoside (α/ß-Man), and ß-galactoside (ß-Gal), was studied by mass spectrometry, 1 Hâ
NMR titrations, and molecular modeling. These studies revealed that selectivity can be achieved in these tetrapodal SCRs by varying the heterocyclic binding group. We found that SCR017 (3-pyrrole), SCR021 (3-pyridine), and SCR022 (2-phenol) bind only to ß-Glc. SCR019 (3-indole) binds only to ß-Man. SCR020 (2-pyridine) binds ß-Man and α-Man with a preference to the latter. SCR018 (2-indole) binds α-Man and ß-Gal with a preference to the former. The glycan guests bound within their SCR hosts in one of three supramolecular geometries center-parallel, center-perpendicular, and off-center. Many host-guest combinations formed higher stoichiometry complexes, 21 glycanâ
SCR or 12 glycanâ
SCR, where the former are driven by positive allosteric cooperativity induced by glycan-glycan contacts.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Polysaccharides
/
Carbohydrates
/
Receptors, Cell Surface
/
Lectins, C-Type
/
Mannose-Binding Lectins
/
Receptors, Artificial
/
Mannose
Type of study:
Experimental Studies
/
Randomized controlled trials
Language:
English
Journal:
Chemistry
Journal subject:
Chemistry
Year:
2020
Document Type:
Article
Affiliation country:
Chem.202000481
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