TY - JOUR
T1 - Gold-phosphine binding to de novo designed coiled coil peptides
AU - Peacock, A.F.A.
AU - Bullen, G.A.
AU - Gethings, L.A.
AU - Williams, J.P.
AU - Kriel, F.H.
AU - Coates, J.
N1 - Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - The coordination of the therapeutically interesting [AuCl(PEt)] to the de novo designed peptide, TRIL23C, under aqueous conditions, is reported here. TRIL23C represents an ideal model to investigate the binding of [AuCl(PEt)] 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(PEt)] was found to react readily with the Cys side chain in a 1:1 ratio as confirmed by UV-visible, P NMR and mass spectrometry. Circular dichroism confirmed that the coiled coil structure was retained on coordination of the {Au(PEt)} 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(PEt)]. 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.
AB - The coordination of the therapeutically interesting [AuCl(PEt)] to the de novo designed peptide, TRIL23C, under aqueous conditions, is reported here. TRIL23C represents an ideal model to investigate the binding of [AuCl(PEt)] 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(PEt)] was found to react readily with the Cys side chain in a 1:1 ratio as confirmed by UV-visible, P NMR and mass spectrometry. Circular dichroism confirmed that the coiled coil structure was retained on coordination of the {Au(PEt)} 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(PEt)]. 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.
UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84869093025&md5=f31702b006e2fe4f18bda73f6a7ba751
U2 - 10.1016/j.jinorgbio.2012.05.010
DO - 10.1016/j.jinorgbio.2012.05.010
M3 - Article
AN - SCOPUS:84869093025
SN - 0162-0134
VL - 117
SP - 298
EP - 305
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
ER -