Synthesis and characterization of a β-hairpin peptide that represents a 'core module' of bovine pancreatic trypsin inhibitor (BPTI)

Natalia Carulla, Clare Woodward, George Barany

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


A new strategy for the design and construction of peptide fragments that can achieve defined, nativelike secondary structure is presented. The strategy is based upon the hypothesis that 'core elements' of a protein, synthesized in a single polypeptide molecule, will favor nativelike structure, and that by incorporating a cross-link, nativelike core structure will dominate the ensemble as the more extended conformations are excluded. 'Core elements' are the elements of packed secondary structure that contain the slowest exchanging backbone amide protons in the native protein. The 'core elements' in bovine pancreatic trypsin inhibitor (BPTI) are the two long strands of antiparallel β-sheet (residues 18 - 24 and 29 - 35) and the small β-bridge (residues 43 - 44). To test the design strategy, we synthesized an 'oxidized core module', which contains the antiparallel strands connected by a modified reverse turn (A27 replaced by D), a natural disulfide cross-link at the open end of the hairpin, and N- and C-termini blocking groups. A peptide with identical sequence but lacking the disulfide cross-link at the open end was used as the 'reduced core module' control. The conformational behavior of both peptides was examined using 1H NMR spectroscopy. Chemical shift dispersion, chemical shift deviation from random coil values, sequential and long-range NOEs, and H/D amide exchange rates were compared for the two peptides. We conclude that the ensemble of oxidized and reduced core module conformations samples both nativelike 4:4 and non- native 3:5 β-hairpin structure, and that the oxidized module samples nativelike structure for a greater fraction of the time than the reduced module.

Original languageEnglish (US)
Pages (from-to)7927-7937
Number of pages11
Issue number27
StatePublished - Jul 11 2000


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