Abstract: A chemoenzymatic method for the preparation of a homogeneous glycoprotein or glycopeptide, including (a) providing an acceptor selected from the group consisting of GlcNAc-protein and GlcNAc-peptide; and (b) reacting the acceptor with a donor substrate including an activated oligosaccharide moiety, in the presence of a catalyst comprising endoglycosidase (ENGase), to transfer the oligosaccharide moiety to the acceptor and yield the homogeneous glycoprotein or glycopeptide. The donor substrate includes, in a specific implementation, a synthetic oligosaccharide oxazoline. A related method of glycoprotein or glycopeptide remodeling with a predetermined natural N-glycan or a tailor-made oligosaccharide moiety, and a method of remodeling an antibody including a heterogeneous sugar chain, are also described. The disclosed methodology enables glycoprotein drugs to be modified for prolonged half-life in vivo, reduced immunogenicity, and enhanced in vivo activity, and for targeting and drug delivery.

Abstract: The present invention relates to a soluble binding complex comprising a soluble gp120 trimer, in which only two gp120 protomers have CD4 binding sites occupied by interconnecting CD4 mimetic moieties, thereby allowing for the exposure of CD4-induced epitopes on the mimetic-bound protomers and an unoccupied CD4 binding site on the third gp120 protomer.

Abstract: The instant invention is drawn to methods of generating a glycosylation-engineered antibody, and using the glycosylation-engineered antibody for treating a patient, particularly a cancer patient or a patient with an immune disease or disorder. The instant invention is also drawn to methods of generating a glycosylation-engineered antibody for use in the treatment of patients having a polymorphism that does not respond to conventional antibody therapy. The instant invention is also drawn to methods of improving the biological activity of an antibody by glycosylation engineering. The instant invention is also drawn to methods of modulating antibody-dependent cell-mediated cytoxicity (ADCC) using a glycosylation-engineered antibody.

Abstract: A method of making a synthetic glycopeptide, by addition of a synthetic oligosaccharide oxazoline to a GlcNAc-containing peptide precursor in the presence of an enzyme selected from among Endo-A and Endo-M. In a specific implementation, the method is utilized to synthesize a trivalent V3-domain glycopeptide including three V3-domain glycopeptides on a scaffold, wherein the three V3-domain glycopeptides are arranged to mimic the V3 domain presentation in trimeric gp120. Such trivalent V3-domain glycopeptides can be utilized in a vaccine for the treatment or prevention of HIV-1 infection.

Abstract: The present invention relates to multivalent HIV inhibitors that bind to multiple sites on a trimeric gp120 complex thereby blocking the CD4 binding site on the trimeric gp120 complex and inhibiting the attachment and entry of HIV through gp120-CD4 interactions.

Abstract: The present invention relates to a constructed oligosaccharide cluster, optionally bonded to an immunogenic protein, that can be administered to a subject to induce an immune response for increasing production of 2G12 and/or used in assays as reactive sites for determining compounds that inactivate and/or bind the high-mannose oligosaccharide cluster. Compositions comprising these clusters, methods of using these clusters and compositions are disclosed.

Abstract: Inhibitors that block the DC-SIGN mediated transmission of the HIV-virus from mucosal infection sites to T-lymphocytes. In one embodiment, the inhibitors include at least one oligosaccharide chain attached to a scaffolding framework in which the number of the oligosaccharide chains attached to the scaffold can be 2, 3, 4 or more. In another embodiment, HIV-I viral infection is treated by administration of a composition including a therapeutically effective amount of an oligosaccharide cluster and/or oligosaccharide/protein cluster binding DC-SIGN, to inhibit DC-SIGN from binding to HIV envelope glycoprotein.

Abstract: Disclosed are scaffolded maleimide clusters, methods of making said clusters and use of said clusters as templates for multivalent peptide assembly. Multiple maleimide functionalities were introduced onto a scaffold molecule by the reaction of a core-centered polyamines with methoxycarbonylmaleimide or with activated esters of maleimide-containing compounds. The scaffolded maleimides allow rapid, highly chemoselective, and high-yield ligation with thiolcontaining peptides under virtually neutral conditions at room temperature. The disclosed 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. These novel scaffolded maleimide clusters allow a highly chemoselective ligation with a thiolcontaining peptide under virtually neutral conditions, providing a new and efficient approach for multivalent peptide assembly.

Abstract: A chemoenzymatic method for the preparation of a homogeneous glycoprotein or glycopeptide, including (a) providing an acceptor selected from the group consisting of GlcNAc-protein and GlcNAc-peptide; and (b) reacting the acceptor with a donor substrate including an activated oligosaccharide moiety, in the presence of a catalyst comprising endoglycosidase (ENGase), to transfer the oligosaccharide moiety to the acceptor and yield the homogeneous glycoprotein or glycopeptide. The donor substrate includes, in a specific implementation, a synthetic oligosaccharide oxazoline. A related method of glycoprotein or glycopeptide remodeling with a predetermined natural N-glycan or a tailor-made oligosaccharide moiety, and a method of remodeling an antibody including a heterogeneous sugar chain, are also described. The disclosed methodology enables glycoprotein drugs to be modified for prolonged half-life in vivo, reduced immunogenicity, and enhanced in vivo activity, and for targeting and drug delivery.

Abstract: A method of making a synthetic glycopeptide, by addition of a synthetic oligosaccharide oxazoline to a GlcNAc-containing peptide precursor in the presence of an enzyme selected from among Endo-A and Endo-M. In a specific implementation, the method is utilized to synthesize a trivalent V3-domain glycopeptide including three V3-domain glycopeptides on a scaffold, wherein the three V3-domain glycopeptides are arranged to mimic the V3 domain presentation in trimeric gp120. Such trivalent V3-domain glycopeptides can be utilized in a vaccine for the treatment or prevention of HIV-1 infection.

Abstract: The present invention relates to a constructed to oligosaccharide cluster, optionally bonded to an immunogenic protein, that can be administered to a subject to induce an immune response for increasing production of 2G12 and/or used in assays as reactive sites for determining compounds that inactivate and/or bind the high-mannose oligosaccharide cluster. Compositions comprising these clusters, methods of using these clusters and compositions are disclosed.

Abstract: The present invention relates to multivalent HIV inhibitors that bind to multiple sites on a trimeric gp120 complex thereby blocking the CD4 binding site on the trimeric gp120 complex and inhibiting the attachment and entry of HIV through gp120-CD4 interactions.

Abstract: Disclosed are scaffolded maleimide clusters, methods of making said clusters and use of said clusters as templates for multivalent peptide assembly. Multiple maleimide functionalities were introduced onto a scaffold molecule by the reaction of a core-centered polyamines with methoxycarbonylmaleimide or with activated esters of maleimide-containing compounds. The scaffolded maleimides allow rapid, highly chemoselective, and high-yield ligation with thiolcontaining peptides under virtually neutral conditions at room temperature. The disclosed 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. These novel scaffolded maleimide clusters allow a highly chemoselective ligation with a thiolcontaining peptide under virtually neutral conditions, providing a new and efficient approach for multivalent peptide assembly.