How changes in the sequence of the peptide CLPFFD-NH2 can modify the conjugation and stability of gold nanoparticles and their affinity for beta-amyloid fibrils.

In a previous work, we studied the interaction of beta-amyloid fibrils (Abeta) with gold nanoparticles (AuNP) conjugated with the peptide CLPFFD-NH2. Here, we studied the effect of changing the residue sequence of the peptide CLPFFD-NH2 on the efficiency of conjugation to AuNP, the stability of the conjugates, and the affinity of the conjugates to the Abeta fibrils. We conjugated the AuNP with CLPFFD-NH 2 isomeric peptides (CDLPFF-NH2 and CLPDFF-NH2) and characterized the resulting conjugates with different techniques including UV-Vis, TEM, EELS, XPS, analysis of amino acids, agarose gel electrophoresis, and CD. In addition, we determined the proportion of AuNP bonded to the Abeta fibrils by ICP-MS. AuNP-CLPFFD-NH2 was the most stable of the conjugates and presented more affinity for Abeta fibrils with respect to the other conjugates and bare AuNP. These findings help to better understand the way peptide sequences affect conjugation and stability of AuNP and their interaction with Abeta fibrils. The peptide sequence, the steric effects, and the charge and disposition of hydrophilic and hydrophobic residues are crucial parameters when considering the design of AuNP peptide conjugates for biomedical applications.

[1]  N. Abbott,et al.  Sequence Dependent Behavior of Amphiphilic β-Peptides on Gold Surfaces , 2007 .

[2]  Edgar Jacoby,et al.  Molecular lipophilicity in protein modeling and drug design. , 2007, Current medicinal chemistry.

[3]  Jesus M de la Fuente,et al.  Tat peptide as an efficient molecule to translocate gold nanoparticles into the cell nucleus. , 2005, Bioconjugate chemistry.

[4]  H. Ohshima,et al.  Colloidal stability of aqueous polymeric dispersions: effect of pH and salt concentration. , 2005, Colloids and surfaces. B, Biointerfaces.

[5]  D. Andreu,et al.  Different immune response of mice immunized with conjugates containing multiple copies of either consensus or mixotope versions of the V3 loop peptide from human immunodeficiency virus type 1. , 2004, Bioconjugate chemistry.

[6]  B. Åkerman,et al.  Electrophoretic properties of DNA-modified colloidal gold nanoparticles. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[7]  M. Brust,et al.  Monolayer Protected Clusters of Gold and Silver , 2004 .

[8]  G. Gordillo,et al.  Adsorption kinetics of charged thiols on gold nanoparticles , 2004 .

[9]  Christopher J. Kiely,et al.  Some recent advances in nanostructure preparation from gold and silver particles: a short topical review , 2002 .

[10]  M. Bear,et al.  Developmental Inhibitory Gate Controls the Relay of Activity to the Superficial Layers of the Visual Cortex , 2001, The Journal of Neuroscience.

[11]  A. Zaman.  Effect of polyethylene oxide on the viscosity of dispersions of charged silica particles: interplay between rheology, adsorption, and surface charge , 2000 .

[12]  J. Nielsen,et al.  Two-Dimensional Cysteine and Cystine Cluster Networks on Au(111) Disclosed by Voltammetry and in Situ Scanning Tunneling Microscopy , 2000 .

[13]  R. Murray,et al.  Monolayer-protected cluster molecules. , 2000, Accounts of chemical research.

[14]  A. M. Alvarez,et al.  Crystal Structures of Molecular Gold Nanocrystal Arrays , 1999 .

[15]  A. McCormick,et al.  A closer look at an aggregation model of the Stober process , 1998 .

[16]  C. Soto,et al.  Inhibition of Alzheimer's amyloidosis by peptides that prevent beta-sheet conformation. , 1996, Biochemical and biophysical research communications.

[17]  Louis A. Cuccia,et al.  Self‐Assembled Monolayers on Gold Nanoparticles , 1996 .

[18]  Ralph G. Nuzzo,et al.  Self-assembled monolayers: Recent developments and applications , 1996 .

[19]  William M. Gelbart,et al.  Thermodynamic Control of Gold Nanocrystal Size: Experiment and Theory , 1995 .

[20]  R. J. Hunter.  Foundations of Colloid Science , 1987 .

[21]  E. Verwey,et al.  Theory of the stability of lyophobic colloids. , 1955, The Journal of physical and colloid chemistry.

[22]  R. Naz,et al.  Peptide vaccines against cancer, infectious diseases, and conception. , 2007, Frontiers in bioscience : a journal and virtual library.

[23]  Antonio Turiel,et al.  Nanoparticle-mediated local and remote manipulation of protein aggregation. , 2006, Nano letters.

[24]  E. Giralt,et al.  Amphipathic peptides and drug delivery. , 2004, Biopolymers.

[25]  D. Astruc,et al.  Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. , 2004, Chemical reviews.

[26]  H. Zeng,et al.  Methodological and chemical factors affecting amyloid beta peptide amyloidogenicity. , 1999, Methods in enzymology.

[27]  E. Kruus,et al.  XPS study of metal-sulfur bonds in metal-alkanethiolate materials , 1998 .

[28]  Mathias Brust,et al.  Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid-liquid system , 1994 .