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Related Experiment Videos

Topochemistry for preparing ligands that dimerize receptors

B A Katz1, R M Stroud, N Collins

  • 1Arris Pharmaceutical Corporation, South San Francisco, CA 94080, USA.

Chemistry & Biology
|September 1, 1995
PubMed
Summary

Protein crystals can mediate chemical reactions. A cyclic peptide within a streptavidin crystal underwent disulfide interchange, forming a dimer. This discovery enables new methods for creating dimeric protein ligands.

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Area of Science:

  • Structural biology
  • Biochemistry
  • Crystallography

Background:

  • A cyclic, disulfide-containing peptide binds streptavidin with high affinity.
  • In streptavidin-peptide cocrystals, monomers are positioned on adjacent tetramers.
  • Crystallographic symmetry places peptide disulfide bonds in close proximity.

Purpose of the Study:

  • To investigate if adjacent peptide disulfide bonds can undergo interchange within a crystal lattice.
  • To determine if this disulfide interchange can lead to peptide dimer formation.
  • To explore the potential for solid-state reactions in protein crystal environments.

Main Methods:

  • Co-crystallization of streptavidin with a cyclic peptide.
  • X-ray crystallography to determine structures of the monomer-bound and dimer-bound crystals.

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  • Independent synthesis and crystallization of the peptide dimer.

    • Main Results:

    • Disulfide interchange occurred between neighboring peptides within the streptavidin crystal lattice, forming a peptide dimer.
    • The peptide dimer adopted the two-fold symmetry of the crystal.
    • The structure of both the monomer and dimer complexes were determined from the same crystal, demonstrating a crystal-mediated transformation.

    Conclusions:

    • Protein crystal lattices can mediate chemical transformations, such as disulfide interchange.
    • This solid-state reaction successfully produced a covalently linked peptide dimer.
    • The peptide dimer can subsequently dimerize streptavidin, suggesting broad utility for preparing dimeric protein ligands.