Design, synthesis and solution structure of a helix–loop–helix dimer—a template for the rational design of catalytically active polypeptides

Abstract

A polypeptide with 42 amino acids, SA-42, has been designed to fold into a 'hairpin' helix-loophelix motif. Its intended use is to serve as a template for the rational design of catalytically active polypeptides. SA-42 is made up of two amphiphilic helices, that are designed to interact through the hydrophobic effect and are connected by a short loop. Evidence is presented that it does adopt the intended motif and that it dimerises in an antiparallel mode at concentrations between 2 pmol dm-3 and 5.6 mmol dmP3. The structural evidence was obtained from NMR and CD spectroscopy and the state of aggregation was determined with equilibrium sedimentation ultracentrifugation and CD spectroscopy. Special attention was paid to the design of SA-42 with respect to the expected NMR spectrum. The mean residue ellipticity at 222 nm of SA-42, -25 000 deg cm2 dmol-', compares well with that of other published helix-loophelices. Two polypeptides that were developed from SA-42 by the replacement of three and five residues, respectively, were recently shown to have catalytical activity .

Self-assembly of synthetic peptides control conformation and optical properties of a zwitterionic polythiophene derivative

“…The absorption maximum (Table 1) is also shifted to a shorter wavelength, thus the polymer backbone adopts a more twisted conformation after formation of the new complex. Because the synthetic peptides have been designed to form a four-helix bundle (21,22), the negatively charged glutamate groups of JR2E will interact with the positively charged lysine groups of JR2K rather than the amino groups of the polymer side chains. Consequently, the interactions responsible for the aggregation of the POWT chains are disrupted.…”

“…This could therefore be used as a platform for making novel sensors and biomolecular switches. In this article we report conformational transitions of a water-soluble, zwitterionic, electroactive, and photoactive polythiophene derivative induced by noncovalent coupling of synthetic peptides designed (21,22) to adopt alternative conformations.…”

Artificial (Pseudo)peptides for Molecular Recognition and Catalysis

“…As a consequence, imine formation is no longer the rate-determining step, which is at variance with the natural enzyme oxaloacetate decarboxylase. Baltzer's group, exploiting the conformational preference of designed 42 amino acid sequences for a helix-loop-helix conformation [77], has systematically modified specific residues in key positions of the oligopeptide to catalyze the hydrolysis and transesterification reactions of p-nitrophenyl esters (Fig. 1.13) [78].…”

Protein design: On the threshold of functional properties

“…altering their properties are the most challenging goals in protein and peptide chemistry. Although in However, the complexity of the molecular organiza-FIGURE 1 Some representative examples of concepts for the de novo design of folding motifs exhibiting tailored functional properties: (a) design of helical bundles from scratch, [4][5][6][7]35 e.g., helix-loop-helix motif taken from Ref. (Figure 1b).…”