Chemoenzymatic Synthesis of HIV-1 V3 Glycopeptides Carrying Two <i>N</i>-Glycans and Effects of Glycosylation on the Peptide Domain

Li, Hengguang; Li, Bing; Song, Haijing; Breydo, Leonid; Baskakov, Ilia V.; Wang, Lai-Xi

doi:10.1021/jo051729z

Cited by 81 publications

(69 citation statements)

References 42 publications

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“…65 The synthesis was achieved by a concise, two-step approach. First, the 47-mer polypeptide that contains two GlcpNAc moieties was prepared by an Fmoc-based solidphase peptide synthesis, using GlcpNAc-Asn as building blocks to introduce the two GlcpNAc tags.…”

Section: Exploring Transition State Analog Substrates For Endoglycosimentioning

confidence: 99%

Chemoenzymatic synthesis of glycopeptides and glycoproteins through endoglycosidase-catalyzed transglycosylation

Wang¹

2008

Carbohydrate Research

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122

113

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Homogeneous glycopeptides and glycoproteins are indispensable for detailed structural and functional studies of glycoproteins. It is also fundamentally important to have to correct glycosylation patterns for developing effective glycoprotein-based therapeutics. This review discusses a useful chemoenzymatic method that takes advantage of the endoglycosidase-catalyzed transglycosylation to attach an intact oligosaccharide to a polypeptide in a single step, without the need for any protecting groups. The exploration of sugar oxazolines (enzymatic reaction intermediates) as donor substrates has not only expanded substrate availability, but also has significantly enhanced the enzymatic transglycosylation efficiency. Moreover, the discovery of a novel mutant with glycosynthase-like activity has made it possible to synthesize homogeneous glycoproteins with full-size natural Nglycans. Recent advances in this highly convergent chemoenzymatic approach and its application for glycopeptide and glycoprotein synthesis are highlighted.

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Section: Exploring Transition State Analog Substrates For Endoglycosimentioning

confidence: 99%

Chemoenzymatic synthesis of glycopeptides and glycoproteins through endoglycosidase-catalyzed transglycosylation

Wang¹

2008

Carbohydrate Research

Self Cite

122

113

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“…[24] Seminal work in the field by Shoda and co-workers demonstrated that carbohydrate oxazolines are useful activated glycosyl donors for these enzymes, presumably since they mimic the putative oxazolinium ions which are intermediates in the enzymatic catalysed hydrolysis reaction. [25] Indeed the efficient synthesis of a series of glycopeptides has been achieved by transglycosylation with Endo A, [26,27] and investigations of a correlation of the efficiency of glycosylation with substrate structure have also been reported. [28] More recent work has also reported the application of the glycoprotein remodelling strategy using Endo A to access single glycoforms of ribonuclease B.…”

Section: Introductionmentioning

confidence: 99%

Endohexosaminidase‐Catalysed Glycosylation with Oxazoline Donors: Fine Tuning of Catalytic Efficiency and Reversibility

Rising

Heidecke

Moir

et al. 2008

Chemistry A European J

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A complete series of oxazoline di-, tri-, tetra-, and hexasaccharides, corresponding to the core sections of N-linked glycoprotein high mannose glycans, together with the corresponding oligosaccharides containing a central glucose unit, were synthesised and tested as glycosyl donors for glycosylation of a GlcNAcAsn glycosyl amino acid catalysed by the endohexosaminidases M (Endo M), A (Endo A) and H (Endo H). Whilst Endo H did not catalyse any glycosylation reactions, both Endo M and Endo A efficiently catalysed glycosylations that were not limited to donors containing the Manbeta(1-->4)GlcNAc linkage. Precise structure activity relationships and time course studies have revealed fine-tuning of the efficiency of the synthetic processes which correlated both with the enzyme used and the precise oxazoline structure. Efficient irreversible glycosylation was achievable with both Endo M and Endo A, further demonstrating the use of structurally modified oxazoline donors as transition state mimics in order to promote enzyme-catalysed synthesis, whilst precluding product hydrolysis; enzymes in these cases display "glycoligase" activity.

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“…Immune escape of the virus from T-cell recognition by point mutation of targeted epitopes may have contributed to the decline seen in these patients. However, escape from T-cell recognition is thought to be most pronounced during the acute and early phases of infection and may subside over the course of simian immunodeficiency virus and HIV infections (5,23,27,29). Most importantly, high plasma loads and low CD4 cell counts at baseline predicted the loss of subdominant Gag responses.…”

Section: Discussionmentioning

confidence: 99%

A High Viral Burden Predicts the Loss of CD8 T-Cell Responses Specific for Subdominant Gag Epitopes during Chronic Human Immunodeficiency Virus Infection

Geldmacher

Gray²,

Nason³

et al. 2007

J Virol

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Human immunodeficiency virus (HIV)-specific CD8 T-cell responses targeting products encoded within theGag open reading frame have frequently been associated with better viral control and disease outcome during the chronic phase of HIV infection. To further clarify this relationship, we have studied the dynamics of Gag-specific CD8 T-cell responses in relation to plasma viral load and time since infection in 33 chronically infected subjects over a 9-month period. High baseline viral loads were associated with a net loss of breadth (P < 0.001) and a decrease in the total magnitude of the Gag-specific T-cell response in general (P ‫؍‬ 0.03). Most importantly, the baseline viral load predicted the subsequent change in the breadth of Gag recognition over time (P < 0.0001, r 2 ‫؍‬ 0.41). Compared to maintained responses, lost responses were low in magnitude (P < 0.0001) and subdominant in the hierarchy of Gag-specific responses. The present study indicates that chronic exposure of the human immune system to high levels of HIV viremia is a determinant of virus-specific CD8 T-cell loss.

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Chemoenzymatic Synthesis of HIV-1 V3 Glycopeptides Carrying Two N-Glycans and Effects of Glycosylation on the Peptide Domain

Cited by 81 publications

References 42 publications

Chemoenzymatic synthesis of glycopeptides and glycoproteins through endoglycosidase-catalyzed transglycosylation

Chemoenzymatic synthesis of glycopeptides and glycoproteins through endoglycosidase-catalyzed transglycosylation

Endohexosaminidase‐Catalysed Glycosylation with Oxazoline Donors: Fine Tuning of Catalytic Efficiency and Reversibility

A High Viral Burden Predicts the Loss of CD8 T-Cell Responses Specific for Subdominant Gag Epitopes during Chronic Human Immunodeficiency Virus Infection

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