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Hyaluronan: the absence of amide-carboxylate hydrogen bonds and the chain conformation in aqueous solution are incompatible with stable secondary and tertiary structure models.

ABSTRACT: Contradictory descriptions for the aqueous solution conformation of the glycosaminoglycan hyaluronan (HA) exist in the literature. According to hydrodynamic and simulation data, HA molecules are stiffened by a rapidly interchanging network of transient hydrogen bonds at the local level and do not significantly associate at the global level. In marked contrast, models derived from NMR data suggest that the secondary structure involves persistent hydrogen bonds and that strong associations between chains can occur to form vast stable tertiary structures. These models require an extended 2-fold helical conformation of the HA chain and specific hydrogen bonds between amide and carboxylate groups. To test these descriptions, we have used 15N-labelled oligosaccharides and high-field NMR to measure pertinent properties of the acetamido group. The amide proton chemical shift perturbation and carboxylate group pK(a) value are inconsistent with a highly populated hydrogen bond between the amide and carboxylate groups. Amide proton temperature coefficients and chemical exchange rates confirm this conclusion. Comparison of oligomer properties with polymeric HA indicates that there is no discernible difference in amide proton environment between the centre of octasaccharides and the polymer, inconsistent with the formation of tertiary structures. A [1H-1H-15N] NOESY-HSQC (heteronuclear single-quantum correlation) spectrum recorded on an HA octasaccharide revealed that amide groups in the centre are in a trans orientation and that the average solution conformation is not an extended 2-fold helix. Therefore the two key aspects of the secondary and tertiary structure models are unlikely to be correct. Rather, these new NMR data agree with descriptions from hydrodynamic and simulations data.

SUBMITTER: Blundell CD

PROVIDER: S-EPMC1482818 | biostudies-other | 2006 Jun

REPOSITORIES: biostudies-other

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Hyaluronan: the absence of amide-carboxylate hydrogen bonds and the chain conformation in aqueous solution are incompatible with stable secondary and tertiary structure models.

Blundell Charles D CD Deangelis Paul L PL Almond Andrew A

The Biochemical journal 20060601 3

Contradictory descriptions for the aqueous solution conformation of the glycosaminoglycan hyaluronan (HA) exist in the literature. According to hydrodynamic and simulation data, HA molecules are stiffened by a rapidly interchanging network of transient hydrogen bonds at the local level and do not significantly associate at the global level. In marked contrast, models derived from NMR data suggest that the secondary structure involves persistent hydrogen bonds and that strong associations between ...[more]

PMID: 16506956

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Project description:Racemization is considered to be an intrinsic stereochemical feature of free radical chemistry as can be seen in traditional radical halogenation reactions of optically active tertiary C-H bonds. If the facile process of radical racemization could be effectively combined with an ensuing step of bond formation in an enantioselective fashion, then it would give rise to deracemizative functionalization of racemic tertiary C-H bonds for stereoselective construction of chiral molecules bearing quaternary stereocenters. As a demonstration of this unique potential in radical chemistry, we herein report that metalloradical catalysis can be successfully applied to devise Co(II)-based catalytic system for enantioconvergent radical amination of racemic tertiary C(sp3)-H bonds. The key to the success of the radical process is the development of Co(II)-based metalloradical catalyst with fitting steric, electronic, and chiral environments of the D2-symmetric chiral amidoporphyrin as the supporting ligand. The existence of optimal reaction temperature is recognized as an important factor in the realization of the enantioconvergent radical process. Supported by an optimized chiral ligand, the Co(II)-based metalloradical system can effectively catalyze the enantioconvergent 1,6-amination of racemic tertiary C(sp3)-H bonds at the optimal temperature, affording chiral α-tertiary amines in excellent yields with high enantiocontrol of the newly created quaternary stereocenters. Systematic studies, including experiments utilizing optically active deuterium-labeled C-H substrates as a model system, shed light on the underlying mechanistic details of this new catalytic process for enantioconvergent radical C-H amination. The remarkable power to create quaternary stereocenters bearing multiple functionalities from ubiquitous C-H bonds, as showcased with stereoselective construction of bicyclic N-heterocycles, opens the door for future synthetic applications of this new radical technology.

Dataset Information

Hyaluronan: the absence of amide-carboxylate hydrogen bonds and the chain conformation in aqueous solution are incompatible with stable secondary and tertiary structure models.

Publications

Hyaluronan: the absence of amide-carboxylate hydrogen bonds and the chain conformation in aqueous solution are incompatible with stable secondary and tertiary structure models.

Similar Datasets

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