Jiahong Ni

Chemoenzymatic Synthesis of HIV-1 gp41 Glycopeptides: Effects of Glycosylation on the Anti-HIV Activity and α-Helix Bundle-Forming Ability of Peptide C34

C34 is a 34‐mer peptide derived from the C‐terminal ectodomain of HIV‐1 envelope glycoprotein, gp41. The C34 region in native gp41 carries a conserved N‐glycan at Asn637 and the sequence is directly involved in the virus–host membrane fusion, an essential step for HIV‐1 infection. This paper describes the synthesis of glycoforms of C34 which carry a monosaccharide, a disaccharide, and a native oligosaccharide moiety. The synthesis of the glycopeptide which carries a native high‐mannose type N‐glycan was achieved by a chemoenzymatic approach by using an endoglycosidase‐catalyzed oligosaccharide transfer as the key step. The effects of glycosylation on the inhibitory activity and the helix‐bundle forming ability of C34 were investigated. It was found that glycosylation moderately decreases the anti‐HIV activity of C34 and, in comparison with C34, glyco‐C34 forms less compact six‐helix bundles with the corresponding N‐terminal peptide, N36. This study suggests that conserved glycosylation modulates the anti‐HIV activity and conformations of the gp41 C‐peptide, C34.

Carbohydrate-Centered Maleimide Cluster as a New Type of Templates for Multivalent Peptide Assembling: Synthesis of Multivalent HIV-1 gp41 Peptides

This paper describes a facile synthesis of carbohydrate-centered maleimide clusters and their application as a new type of templates for multivalent peptide assembling. Simultaneous introduction of multiple maleimide functionalities onto a carbohydrate core was achieved through the reaction of carbohydrate-based polyamines with methoxycarbonylmaleimide or with the N-hydroxylsuccinimide ester of 6-maleimidohexanoic acid. The clustered maleimides placed on the carbohydrate core allow rapid and highly chemoselective ligation with multiple copies of cysteine-containing peptides under virtually neutral conditions at room temperature. This mild and highly efficient ligation method is extremely valuable for synthesizing large and complex multivalent peptides that may not be easily obtained by conventional ligation methods. The usefulness of the maleimide clusters as a new type of templates for multivalent peptide synthesis was exemplified by the synthesis of two tetravalent gp41 peptides incorporating the sequence of the potent HIV inhibitor, T20. The synthetic multivalent gp41 peptides are useful as novel immunogens to raise specific antibodies for HIV studies. They are also useful probes for studying HIV membrane fusion mechanisms.

Chemoenzymatic synthesis of high-mannose type HIV-1 gp120 glycopeptides.

A chemoenzymatic approach to the synthesis of glycoforms of HIV-1 gp120 glycopeptides is described. Thus, the high-mannose type glycopeptides [gp120 (336-342)] containing Man(9), Man(6) and Man(5) moieties, respectively, were synthesized in satisfactory yields via transglycosylation to the acetylglucosaminyl peptide, using the recombinant Arthrobacter Endo-beta-N-acetyl-glucosaminidase (Endo-A) as the key enzyme.

Improved preparation of perallylated cyclodextrins: facile synthesis of cyclodextrin-based polycationic and polyanionic compounds

An improved procedure for the perallylation of cyclodextrins allowed the preparation of O-perallylated alpha-, beta-, and gamma-cyclodextrins in 89, 91, and 88% yields, respectively. These were converted into two cyclodextrin-based functionalized compounds, the polycationic heptakis[2,3,6-tri-O-(6-amino-3-thiahexyl)]-beta-cyclodextrin hydrochloride (3), and the polyanionic heptakis[2,3,6-tri-O-(sodium 5-carboxyl-3-thiapentyl)]-beta-cyclodextrin (4), a potential inhibitor of HIV-1 replication.