A Linear Synthesis of Branched High-Mannose Oligosaccharides from the HIV-1 Viral Surface Envelope Glycoprotein gp120

Described is a linear solution-phase synthesis of the HIV-1 viral surface envelope glycoprotein gp120 high-mannose nonasaccharide pentyl glycoside. Envisioning the automated solid-phase assembly of complex carbohydrates, the synthesis of the nonasaccharide and the related tri- and hexamannosides demonstrates the facile assembly of highly branched structures in a stepwise fashion incorporating monosaccharide building blocks. A differentially protected core trisaccharide was prepared and further elongated in two high-yielding tri-mannosylations to furnish the triantennary structure. The tri-, hexa-, and nonamannoside n-pentyl glycosides obtained via the described synthesis are currently being used for detailed study of the carbohydrate protein interactions responsible for binding of the anti-HIV protein cyanovirin-N to the glycoprotein gp120. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

[1]  C. Bewley,et al.  The potent anti-HIV protein cyanovirin-N contains two novel carbohydrate binding sites that selectively bind to Man(8) D1D3 and Man(9) with nanomolar affinity: implications for binding to the HIV envelope protein gp120. , 2001, Journal of the American Chemical Society.

[2]  P. Konradsson,et al.  Use of n-pentenyl glycosides as precursors to various spacer functionalities. , 2000, The Journal of organic chemistry.

[3]  B. Fraser-Reid,et al.  n-Pentenyl Mannoside Precursors for Synthesis of the Nonamannan Component of High Mannose Glycoproteins , 1994 .

[4]  M. Boyd,et al.  Cyanovirin-N, a Potent Human Immunodeficiency Virus-Inactivating Protein, Blocks both CD4-Dependent and CD4-Independent Binding of Soluble gp120 (sgp120) to Target Cells, Inhibits sCD4-Induced Binding of sgp120 to Cell-Associated CXCR4, and Dissociates Bound sgp120 from Target Cells , 2001, Antimicrobial Agents and Chemotherapy.

[5]  E. Freed,et al.  The Role of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins in Virus Infection (*) , 1995, The Journal of Biological Chemistry.

[6]  P. Seeberger,et al.  Solid-phase oligosaccharide synthesis: preparation of complex structures using a novel linker and different glycosylating agents. , 1999, Organic letters.

[7]  G. Müller,et al.  Structure-activity relationship of synthetic phosphoinositolglycans mimicking metabolic insulin action. , 1998, Biochemistry.

[8]  R. Madsen,et al.  n-Pentenyl Glycosides in Organic Chemistry: A Contemporary Example of Serendipity , 1992 .

[9]  K. Liu,et al.  Route from Glycals to Mannose .beta.-Glycosides , 1994 .

[10]  R. Schmidt,et al.  Synthesis of a GPI Anchor of Yeast (Saccharomyces cerevisiae) , 1994 .

[11]  S. Danishefsky,et al.  Pursuit of optimal carbohydrate-based anticancer vaccines: preparation of a multiantigenic unimolecular glycopeptide containing the Tn, MBr1, and Lewis(y) antigens. , 2001, Journal of the American Chemical Society.

[12]  S. Ley,et al.  Synthesis of the Nonamannan Residue of a Glycoprotein with High Mannose Content , 1996 .

[13]  A. Gronenborn,et al.  Solution structure of cyanovirin-N, a potent HIV-inactivating protein , 1998, Nature Structural Biology.

[14]  C. Bewley,et al.  Rapid validation of the overall structure of an internal domain-swapped mutant of the anti-HIV protein cyanovirin-N using residual dipolar couplings. , 2001, Journal of the American Chemical Society.

[15]  M. Matsui,et al.  Synthetic studies on cell surface glycans 31: Branching pentasaccharides of glycoprotein , 1981 .

[16]  P. Seeberger,et al.  Halobenzyl Ethers as Protecting Groups for Organic Synthesis , 2000 .

[17]  J. Rademann,et al.  Solid-Phase Supported Synthesis of the Branched Pentasaccharide Moiety That Occurs in Most Complex Type N-Glycan Chains. , 1998, Angewandte Chemie.

[18]  S. Nakabayashi,et al.  Synthesis of a hexasaccharide unit of a complex type of glycan chain of a glycoprotein. , 1981, Carbohydrate research.

[19]  S. Danishefsky,et al.  Glycals in Organic Synthesis: The Evolution of Comprehensive Strategies for the Assembly of Oligosaccharides and Glycoconjugates of Biological Consequence , 1996 .

[20]  L K Pannell,et al.  Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development , 1997, Antimicrobial agents and chemotherapy.

[21]  S. Ley,et al.  1,2-diacetals: a new opportunity for organic synthesis. , 2001, Chemical reviews.

[22]  M. Boyd,et al.  Analysis of the interaction between the HIV-inactivating protein cyanovirin-N and soluble forms of the envelope glycoproteins gp120 and gp41. , 2000, Molecular pharmacology.

[23]  T. Nukada,et al.  Synthesis of a branched mannohexaoside, a part structure of a high-mannose-type glycan of a glycoprotein , 1985 .

[24]  T. Ogawa,et al.  Synthesis of a branched d-mannopentaoside and a branched d-mannohexaoside: Models of the outer chain of the glycan of soybean agglutinin , 1981 .