Solid-phase synthesis and screening of a library of C-terminal arginine peptide aldehydes against Murray Valley encephalitis virus protease.

Murray Valley encephalitis virus is a member of the flavivirus group, a large family of single-stranded RNA viruses, which cause serious disease in all regions of the world. Unfortunately, no suitable antivirals are available, and there are commercial vaccines for only three flaviviruses. The solid-phase synthesis of a library of 400 C-terminal arginine peptide aldehydes and their screening against Murray Valley encephalitis virus protease are demonstrated. The library was utilised to elucidate several tripeptide sequences that can be used as inhibitors in further SAR studies.

Complexity in nanoparticle assembly and function obtained by direct-grafted peptides.

We synthesize peptide-functionalized nanoparticles by growing the peptide directly from the nanoparticles in a grafting-from process. We demonstrate the procedure by grafting a short, pH and oxidation responsive peptide sequence from 300 nm silica nanoparticles. The peptide allows destabilization of the particles in response to pH by neutralization of electrostatic charge, while manipulation of oxidizing conditions in the system offers the ability to select for irreversible, covalent bonding between the particles. In one system, we show the assembly of an asymmetrically functionalized set of particles, which may have applications in the formation of binary particle networks. The method of preparing peptide-coated particles should greatly simplify existing processes used to create peptide-functionalized nanoparticles.

Peptides grafted from solids for the control of interfacial properties.

We have used solid-phase peptide synthesis to graft a peptide monolayer from a solid in order to modify the interfacial properties. We grafted a 15-residue peptide, EKEKEKEKEKEKEGG, containing a zwitterionic sequence of alternating lysine and glutamic acid residues from the surface of an aminosilanized silicon wafer by placing the silicon wafer within a commercial microwave peptide synthesizer. Such synthesizers are routinely used to make peptides on porous beads, but the peptides are subsequently cleaved and used independently of the solid support; our aim is to utilize the covalently bound peptide to control the surface properties without the need for cleavage and reattachment. We confirmed the presence of this peptide layer on the surface by X-ray photoelectron spectroscopy and ellipsometry. Atomic force microscopy was then used to study the forces between the peptide-modified surface and a borosilicate glass sphere as a function of the solution pH. The adsorbed peptide makes the silicon wafer pH responsive: at high pH the glass particle is repelled from the wafer, and at low pH it is attracted. Previous studies with synthetic polymers have shown that the "grafting from" method allows a much higher film density than "grafting to". We propose that the application of grafting from strategies to peptide layers may offer three additional benefits: (1) the film density can be controlled independently of the primary sequence of the peptide, (2) the sequence constraints for spontaneous adsorption are removed, and (3) the procedure is fast and efficient, which may lead to lower costs and the ability for high-throughput surface biofunctionalization. Moreover, peptide layers offer increased sequence diversity, control, and functionality compared to conventional polymer brushes.