Structural and kinetic analyses of holothurian sulfated glycans suggest potential treatment for SARS-CoV-2 infection.

Certain sulfated glycans, including those from marine sources, can show potential effects against SARS-CoV-2. Here, a new fucosylated chondroitin sulfate (FucCS) from the sea cucumber Pentacta pygmaea (PpFucCS) (MW ∼10-60 kDa) was isolated and structurally characterized by NMR. PpFucCS is composed of {→3)-β-GalNAcX-(1→4)-β-GlcA-[(3→1)Y]-(1→}, where X = 4S (80%), 6S (10%) or nonsulfated (10%), Y = α-Fuc2,4S (40%), α-Fuc2,4S-(1→4)-α-Fuc (30%), or α-Fuc4S (30%), and S = SO.

Negative allosteric modulators of cannabinoid receptor 1: Ternary complexes including CB1, orthosteric CP55940 and allosteric ORG27569.

In October 2019, the first X-ray crystal structure of a ternary cannabinoid receptor 1 (CB1) complex (PDB ID: 6KQI) was published, including the well-known orthosteric agonist, CP55940, and the well-studied negative allosteric modulator, ORG27569. Prior to the release of 6KQI, we applied binding pocket analysis and molecular docking to carefully prepared computational models of the ternary CB1 complex, in order to predict the binding site for ORG27569 with the CP55940-bound CB1 receptor. We carefully studied the binding pose of agonist ligands in the CB1 orthosteric pocket, including CP55940.

Conformational properties of l-fucose and the tetrasaccharide building block of the sulfated l-fucan from Lytechinus variegatus.

Although the 3D structure of carbohydrates is known to contribute to their biological roles, conformational studies of sugars are challenging because their chains are flexible in solution and consequently the number of 3D structural restraints is limited. Here, we investigate the conformational properties of the tetrasaccharide building block of the Lytechinus variegatus sulfated fucan composed of the following structure [l-Fucp4(SO)-α(1-3)-l-Fucp2,4(SO)-α(1-3)-l-Fucp2(SO)-α(1-3)-l-Fucp2(SO)] and the composing monosaccharide unit Fucp, primarily by nuclear magnetic resonance (NMR) experiments performed at very low temperatures and using HO as the solvent for the sugars rather than using the conventional deuterium oxide. By slowing down the fast chemical exchange rates and forcing the protonation of labile sites, we increased the number of through-space H-H distances that could be measured by NMR spectroscopy.