Design, synthesis and evaluation of synthetic receptors for the recognition of aspartate pairs in an α-helical confirmation

Jeffrey S. Albert, Mark W. Peczuh, Andrew Hamilton

Research output: Contribution to journalArticle

Abstract

The specific targeting of protein surface functional groups remains a largely unexplored aspect in molecular recognition. In this study, a series of zwitterionic, 16-mer peptides serve as models for the recognition of carboxylate pairs in proteins. A receptor is described that contains two guanidinium groups separated by 4-5 Å by a rigid bicyclo[3.3.0]octane spacer. Modeling studies indicate that such a receptor would be suitable for binding with two aspartate carboxylates when the amino acids are separated by two (i+3) or three (i+4) other amino acids in an α-helical peptide. Studies employing circular dichroism spectroscopy demonstrated that the addition of the receptor to the i+3 peptide substrate caused a 23% enhancement of helical structure in 15% water/methanol at 25°C. Other substrate peptides [(i+1), (i+4), (i+7), (i+10)] showed lower helical induction. Similar, but weaker binding and helical induction were observed under buffered conditions (10 mM Tris-Mes, pH 7.0). These results, along with studies employing a series of related di-cationic receptors, suggest a 1:1 binding model composed of specific hydrogen interactions between each receptor guanidinium with each substrate carboxylate when the peptide adopts a helical conformation.

Original languageEnglish (US)
Pages (from-to)1455-1467
Number of pages13
JournalBioorganic and Medicinal Chemistry
Volume5
Issue number8
DOIs
StatePublished - Aug 1997

Fingerprint

Artificial Receptors
Aspartic Acid
Peptides
Guanidine
Substrates
Circular dichroism spectroscopy
Amino Acids
Molecular recognition
Protein Transport
Circular Dichroism
Functional groups
Methanol
Conformations
Hydrogen
Spectrum Analysis
Membrane Proteins
Water
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Design, synthesis and evaluation of synthetic receptors for the recognition of aspartate pairs in an α-helical confirmation. / Albert, Jeffrey S.; Peczuh, Mark W.; Hamilton, Andrew.

In: Bioorganic and Medicinal Chemistry, Vol. 5, No. 8, 08.1997, p. 1455-1467.

Research output: Contribution to journalArticle

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