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Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands.

Publication ,  Journal Article
Debenham, SD; Snyder, PW; Toone, EJ
Published in: The Journal of organic chemistry
July 2003

The development of carbohydrate-based therapeutics has been frustrated by the low affinities that characterize protein-carbohydrate complexation. Because of the oligomeric nature of most lectins, the use of multivalency may offer a successful strategy for the creation of high-affinity ligands. The solid-phase evaluation of libraries of peptide-linked multivalent ligands facilitates rapid examination of a large fraction of linker structure space. If such solid-phase assays are to replicate solution binding behavior, the potential for intermolecular bivalent binding on bead surfaces must be eliminated. Here we report the solid-phase synthesis and analysis of peptide-linked, spatially segregated mono- and bivalent ligands for the legume lectin concanavalin A. Bead shaving protocols were used for the creation of beads displaying spatially segregated binding sequences on the surface of Tentagel resins. The same ligands were also synthesized on PEGA resin to determine the effect of ligand presentation on solid-phase binding. While we set out to determine the lower limit of assay sensitivity, the unexpected observation that intermolecular bivalent ligand binding is enhanced for bivalent ligands relative to monovalent ligands allowed direct observation of the level of surface blocking required to prevent intermolecular bivalent ligand binding. For a protein with binding sites separated by 65 A, approximately 99.9% of Tentagel(1) surface sites and 99.99% of the total sites on a PEGA bead must be blocked to prevent intermolecular bivalent binding. We also report agglutination and calorimetric solution-phase binding studies of mono- and bivalent peptide-linked ligands.

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Published In

The Journal of organic chemistry

DOI

EISSN

1520-6904

ISSN

0022-3263

Publication Date

July 2003

Volume

68

Issue

15

Start / End Page

5805 / 5811

Related Subject Headings

  • Organic Chemistry
  • Oligopeptides
  • Magnetic Resonance Spectroscopy
  • Ligands
  • Lectins
  • Kinetics
  • Indicators and Reagents
  • Humans
  • Hemagglutination Tests
  • Concanavalin A
 

Citation

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Debenham, S. D., Snyder, P. W., & Toone, E. J. (2003). Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands. The Journal of Organic Chemistry, 68(15), 5805–5811. https://doi.org/10.1021/jo0207271
Debenham, Sheryl D., Phillip W. Snyder, and Eric J. Toone. “Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands.The Journal of Organic Chemistry 68, no. 15 (July 2003): 5805–11. https://doi.org/10.1021/jo0207271.
Debenham SD, Snyder PW, Toone EJ. Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands. The Journal of organic chemistry. 2003 Jul;68(15):5805–11.
Debenham, Sheryl D., et al. “Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands.The Journal of Organic Chemistry, vol. 68, no. 15, July 2003, pp. 5805–11. Epmc, doi:10.1021/jo0207271.
Debenham SD, Snyder PW, Toone EJ. Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands. The Journal of organic chemistry. 2003 Jul;68(15):5805–5811.
Journal cover image

Published In

The Journal of organic chemistry

DOI

EISSN

1520-6904

ISSN

0022-3263

Publication Date

July 2003

Volume

68

Issue

15

Start / End Page

5805 / 5811

Related Subject Headings

  • Organic Chemistry
  • Oligopeptides
  • Magnetic Resonance Spectroscopy
  • Ligands
  • Lectins
  • Kinetics
  • Indicators and Reagents
  • Humans
  • Hemagglutination Tests
  • Concanavalin A