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Volume 92 Issue 13 | p. 24 | Concentrates
Issue Date: March 31, 2014

Technique Sifts Through Possible Leads For HIV Vaccines

Adaptation of mRNA display selects glycopeptides that tightly bind an HIV-neutralizing antibody
Department: Science & Technology
News Channels: Biological SCENE, JACS In C&EN
Keywords: HIV, glycopeptide, carbohydrate chemistry, vaccine, directed evolution, mRNA display

Researchers know of roughly two dozen antibodies capable of neutralizing a broad range of HIV strains. People with HIV rarely make them quickly enough to contain infection, so the search continues for a vaccine that goads immune systems into production mode. Several neutralizing anti­bodies bind to sugars on the virus, so some experts think that a glycopeptide vaccine that mimics HIV’s sugar-coated surface might work. It has proven challenging, however, to cluster carbohydrates in the right spatial arrangement. To rapidly sift through glycopeptide possibilities, Satoru Horiya, Isaac J. Krauss, and colleagues at Brandeis University collaborated with Yollete V. Guillen Schlippe at Massachusetts General Hospital. They adapted mRNA display, a technique that attaches RNA bar codes to library peptides, to select tight binders to HIV antibody 2G12. They encoded copies of an unnatural amino acid as attachment points for sugars and attached them with click chemistry. They found glycopeptides that bind 2G12 with low nanomolar affinity—comparable to the strength of the HIV-2G12 interaction (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja500678v). Now they plan to see whether their glycopeptides elicit an immune response in animals. Krauss has filed a patent on the technology.

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Each glycopeptide (structures and red circles) in the library is linked to RNA (green line) via the nucleoside puromycin (blue circle). cDNA is shown as a red line.
Credit: Courtesy of Isaac Krauss
09213-scicon-glycopeptide
 
Each glycopeptide (structures and red circles) in the library is linked to RNA (green line) via the nucleoside puromycin (blue circle). cDNA is shown as a red line.
Credit: Courtesy of Isaac Krauss
 
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