Dataset Information

Side Chain Conformation and Its Influence on Glycosylation Selectivity in Hexo- and Higher Carbon Furanosides.

ABSTRACT: We describe the synthesis and side chain conformational analysis of a series of four 6-deoxy-2,3,5-tri-O-benzyl hexofuranosyl donors with the d-gluco, l-ido, d-altro, and l-galacto configurations. The conformation of the exocyclic bond of these compounds depends on the relative configuration of the point of attachment of the side chain to the ring and of the two flanking centers and can be predicted on that basis analogously to the heptopyranose analogs. Variable-temperature nuclear magnetic resonance (VT NMR) spectroscopy of the activated donors reveals complex, configuration-dependent mixtures of intermediates that we interpret in terms of fused and bridged oxonium ions arising from participation by the various benzyl ethers. The increased importance of ether participation in the furanoside series compared to the pyranosides is discussed in terms of the reduced stabilization afforded to furanosyl oxocarbenium ions by covalent triflate formation. The stereoselectivities of the four donors are discussed on the basis of the benzyl ether participation model.

SUBMITTER: Siyabalapitiya Arachchige S

PROVIDER: S-EPMC8741747 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Side Chain Conformation and Its Influence on Glycosylation Selectivity in Hexo- and Higher Carbon Furanosides.

Siyabalapitiya Arachchige Sameera S Crich David D

The Journal of organic chemistry 20211214 1

We describe the synthesis and side chain conformational analysis of a series of four 6-deoxy-2,3,5-tri-<i>O</i>-benzyl hexofuranosyl donors with the d-gluco, l-ido, d-altro, and l-galacto configurations. The conformation of the exocyclic bond of these compounds depends on the relative configuration of the point of attachment of the side chain to the ring and of the two flanking centers and can be predicted on that basis analogously to the heptopyranose analogs. Variable-temperature nuclear magne ...[more]

PMID: 34905382

Similar Datasets

Project description:Whether synaptic transmission is excitatory or inhibitory depends, to a large extent, on whether the ion channels that open upon binding the released neurotransmitter conduct cations or anions. The mechanistic basis of the opposite charge selectivities of Cys-loop receptors has only recently begun to emerge. It is now clear that ionized side chains-whether pore-facing or buried-in the first α-helical turn of the second transmembrane segments underlie this phenomenon and that the electrostatics of backbone atoms are not critically involved. Moreover, on the basis of electrophysiological observations, it has recently been suggested that not only the sign of charged side chains but also their conformation are crucial determinants of cation-anion selectivity. To challenge these ideas with the chemical and structural rigor that electrophysiological observations naturally lack, we performed molecular dynamics, Brownian dynamics, and electrostatics calculations of ion permeation. To this end, we used structural models of the open-channel conformation of the α1 glutamate-gated Cl- channel and the α1 glycine receptor. Our results provided full support to the notion that the conformation of charged sides chains matters for charge selectivity. Indeed, whereas some rotamers of the buried arginines at position 0' conferred high selectivity for anions, others supported the permeation of cations and anions at similar rates or even allowed the faster permeation of cations. Furthermore, we found that modeling glutamates at position -1' of the anion-selective α1 glycine receptor open-state structure-instead of the five native alanines-switches charge selectivity also in a conformation-dependent manner, with some glutamate rotamers being much more effective at conferring selectivity for cations than others. Regarding pore size, we found that the mere expansion of the pore has only a minimal impact on cation-anion selectivity. Overall, these results bring to light the previously unappreciated impact of side-chain conformation on charge selectivity in Cys-loop receptors.

Dataset Information

Side Chain Conformation and Its Influence on Glycosylation Selectivity in Hexo- and Higher Carbon Furanosides.

Publications

Side Chain Conformation and Its Influence on Glycosylation Selectivity in Hexo- and Higher Carbon Furanosides.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets