engineering-antiviral-agents-via-surface-plasmon-resonance

Engineering Antiviral Agents <em>via</em> Surface Plasmon Resonance

Surface plasmon resonance (SPR) is used to measure hemagglutinin (HA) binding to domain-swapped Cyanovirin-N (CV-N) dimer and to monitor interactions ...

University of California, Los Angeles

Medical University of Vienna

Cyanovirin-N (CV-N) has been shown to reveal broad neutralizing activity against human immunodeficiency virus (HIV) and to specifically bind Manα(1→2)Manα units exposed on various glycoproteins of enveloped viruses, such as influenza hemagglutinin (HA) and Ebola glycoprotein. Chemically synthesized dimannosylated HA peptides bound domain-swapped and dimeric CV-N with either four disulfide-bonds (Cys-Cys), or three Cys-Cys bonds and an intact fold of the high-affinity binding site at an equilibrium dissociation constant   of 10 μM. Cys-Cys mutagenesis with ion-pairing amino-acids glutamic acid and arginine was calculated by  structure-based protein design and allowed for recognizing dimannose and dimannosylated peptide binding to low-affinity binding sites (  ≈ 11 μM for one C58-C73 bond, and binding to dimannosylated peptide). In comparison, binding to HA was achieved based on one ion-pairing C58E-C73R substitution at   = 275 nM, and   = 5 μM for two C58E-C73R substitutions. We were utilizing a triazole bioisostere linkage to form the respective mannosylated-derivative on the HA peptide sequence of residues glutamine, glycine, and glutamic acid. Thus, mono- and dimannosylated peptides with N-terminal cysteine facilitated site-specific interactions with HA peptides, mimicking a naturally found N-linked glycosylation site on the HA head domain.

Irene Maier

Department of Environmental Health Sciences

University of California, Los Angeles

Engineering Antiviral Agents via Surface Plasmon Resonance

Irene Maier

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Environmental Health Sciences

University of California, Los Angeles

Engineering Antiviral Agents via Surface Plasmon Resonance

Department of Environmental Health Sciences