Gold-phosphine binding to de novo designed coiled coil peptides

• Published in: Journal of inorganic biochemistry 2012-12, Vol.117, p.298-305
• Main Authors: Peacock, Anna F.A., Bullen, Gemma A., Gethings, Lee A., Williams, Jonathan P., Kriel, Frederik H., Coates, Judy
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Auranofin; Circular Dichroism; Coiled coil; Coordination Complexes - chemistry; De novo peptide; Gold - chemistry; Gold phosphine; Models, Molecular; Molecular Sequence Data; Organogold Compounds - chemistry; Peptides - chemistry; Phosphines - chemistry; Protein Conformation; Protein design; Protein Folding; Protein Structure, Secondary; Spectrometry, Mass, Electrospray Ionization
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2012.05.010

The coordination of the therapeutically interesting [AuCl(PEt3)] to the de novo designed peptide, TRIL23C, under aqueous conditions, is reported here. TRIL23C represents an ideal model to investigate the binding of [AuCl(PEt3)] to small proteins in an effort to develop novel gold(I) phosphine peptide adducts capable of mimicking biological recognition and targeting. This is due to the small size of TRIL23C (30 amino acids), yet stable secondary and tertiary fold, symmetric nature and the availability of only one thiol binding site. [AuCl(PEt3)] was found to react readily with the Cys side chain in a 1:1 ratio as confirmed by UV-visible, 31P NMR and mass spectrometry. Circular dichroism confirmed that the coiled coil structure was retained on coordination of the {Au(PEt3)}+ unit. Redesign of the exterior of TRIL23C based on a biologically relevant recognition sequence found in GCN4, did not alter the coordination chemistry of [AuCl(PEt3)]. To the best of our knowledge, this represents the first report on the coordination of gold(I) phosphine compounds to de novo designed peptides, and could lead to the generation of novel gold(I) phosphine peptide therapeutics in the future. The coordination of gold triethylphosphine through the cysteine side chain of a de novo designed coiled coil peptide has been investigated under mild aqueous conditions. The secondary structure is retained in the gold–peptide adduct and could ultimately be exploited to develop novel gold–peptide therapeutics capable of biomolecular recognition. [Display omitted]