Stabilizing effect of a multiple salt bridge in a prenucleated peptide

Leland Mayne, S. Walter Englander, Rong Qiu, Jianxin Yang, Youxiang Gong, Erik J. Spek, Neville R. Kallenbach

Research output: Contribution to journalArticle

Abstract

The free energy contribution of salt bridges to protein stability remains a controversial issue. The role of single salt bridges has been investigated in protein and peptide studies; there is no reported value of a multiple salt bridge employing peptide models. We have designed a de novo peptide model to evaluate the strength of a multiple salt bridge. Measurement of the rate of hydrogen exchange (HX) of the backbone NH groups in α- helical peptides allows determination of the absolute free energy of individual interactions that participate in helix stabilization. We apply this procedure here to evaluate the stabilizing contribution of a multiple salt bridge involving Glu3, Asp4, and Arg7 in an 11-mer peptide. The peptide is prenucleated by a lactam bridge connecting two side chains spaced four residues apart. Measurement of the HX rates of each NH group in this peptide as a function of pH, together with the pH independent rate of a Gln3 and Asn4 analogue, reveals a substantial favorable contribution to the α-helix from the salt bridge: ΔG°= -1.2 ± 0.2 kcal/mol. This is the first evaluation of the strength of an engineered complex salt bridge in a peptide and yields a high value, comparable to results of mutation studies on proteins.

Original languageEnglish (US)
Pages (from-to)10643-10645
Number of pages3
JournalJournal of the American Chemical Society
Volume120
Issue number41
DOIs
StatePublished - Oct 21 1998

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Mayne, L., Englander, S. W., Qiu, R., Yang, J., Gong, Y., Spek, E. J., & Kallenbach, N. R. (1998). Stabilizing effect of a multiple salt bridge in a prenucleated peptide. Journal of the American Chemical Society, 120(41), 10643-10645. https://doi.org/10.1021/ja981592c