Secondary structure of a dynamic type I’β-hairpin peptide

  1. C.E. Stotz,
  2. R.T. Borchardt,
  3. C.R. Middaugh,
  4. T.J. Siahaan,
  5. D. Vander Velde,
  6. E.M. Topp

Article first published online: 20 APR 2004

DOI: 10.1111/j.1399-3011.2004.00129.x

Issue

The Journal of Peptide Research

The Journal of Peptide Research

Volume 63, Issue 4, pages 371–382, April 2004

Additional Information

How to Cite

Stotz, C.E., Borchardt, R.T., Middaugh, C.R., Siahaan, T.J., Vander Velde, D. and Topp, E.M. (2004), Secondary structure of a dynamic type I’β-hairpin peptide. The Journal of Peptide Research, 63: 371–382. doi: 10.1111/j.1399-3011.2004.00129.x

Author Information

  1. C.E. Stotz, R.T. Borchardt, C.R. Middaugh, T.J. Siahaan, D. Vander Velde and E.M. Topp, Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047, USA.

*Elizabeth M. Topp Department of Pharmaceutical Chemistry The University of Kansas 2095 Constant Avenue Lawrence KS 66047 USA Tel.: (785) 864-3644 Fax: (785) 864-5736 E-mail: topp@ku.edu

Publication History

  1. Issue published online: 8 DEC 2008
  2. Article first published online: 20 APR 2004
  3. Dates: Received 20 August 2003 Revised 12 December 2003 Accepted 21 December 2003

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Keywords:

  • β-hairpin;
  • β-turn;
  • circular dichroism;
  • nuclear magnetic resonance;
  • peptide;
  • secondary structure

Abstract:  A spontaneously folding β-hairpin peptide (Lys-Lys-Tyr-Thr-Val-Ser-Ile-Asn-Gly-Lys-Lys-Ile-Thr-Val-Ser-Ile) and related cyclic (cyclo-Gly-Lys-Tyr-Ile-Asn-Gly-Lys-Ile-Ile-Asn) and linear (Ser-Ile-Asn-Gly-Lys) controls were studied to determine the effects of various factors on secondary structure. Secondary structure was evaluated using circular dichroism (CD) and 1D and 2D 1H nuclear magnetic resonance (NMR). The effects of chemical modifications in the peptide and various solution conditions were investigated to determine their impact on peptide structure. The β-hairpin peptide displayed a CD minimum at 216 nm and a TOCSY i + 1 − i + 2 and i + 2 −i + 3 interaction, confirming the expected structure. Using NMR α-proton (H) chemical shifts, the extents of folding of the β-hairpin and linear control were estimated to be 51 and 25% of the cyclic control (pH 4, 37 °C), which was taken to be maximally folded. Substitution of iso-aspartic acid for Asn reduced the secondary structure dramatically; substitution of aspartic acid for Asn also disrupted the structure. This result suggests that deamidation in unconstrained β-turns may have adverse effects on secondary structure. N-terminal acetylation and extreme pH conditions also reduced structure, while the addition of methanol increased structure.

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