A loop corresponding to residues 8–17 in the polypeptide cardiac stimulant anthopleurin‐A is known to be important for the cardiostimulant activity of this molecule. To investigate the activity and possible conformations of this loop in isolation, two synthetic peptides have been studied. The first corresponds to residues 6–20 of anthopleurin‐A with Cys6 replaced by Thr, and the second to residues 6–21 of anthopleurin‐A, with Thr21 replaced by Cys. The introduction of an additional cysteine in the latter peptide enabled an intramolecular disulfide to be formed between the N‐ and C‐terminal residues. Both linear peptides and the disulfide‐containing analogue lack the cardiostimulant and Na+‐channel binding activity of the parent molecule, anthopleurin‐A, indicating that although the loop is important for the function of anthopleurin‐A, other regions of the molecule must also be involved in activity. Assignments of the 1H‐NMR spectra of both peptides are presented, and their pH and temperature dependences investigated. The results show that the amide protons of Gly5 and Asn11 (corresponding to Gly10 and Asn16 in anthopleurin‐A) sample hydrogen‐bonded conformations in solution. Based on these NMR data, two regions of non‐random structure, encompassing residues 2–5 and 8–11, respectively, are proposed, and the possible involvement of such structures in the activity of anthopleurin‐A is discussed.
|Number of pages||11|
|Journal||European Journal of Biochemistry|
|Publication status||Published - 1992|