Polyglycine II Nanosheets: Supramolecular Antivirals?

Abstract

Tetraantennary peptides [glycine(n)-NHCH(2)](4)C can form stable noncovalent structures by self-assembly through intermolecular hydrogen bonding. The oligopeptide chains assemble as polyglycine II to yield submicron-sized, flat, one-molecule-thick sheets. Attachment of alpha-N-acetylneuraminic acid (Neu5Acalpha) to the terminal glycine residues gives rise to water-soluble assembled glycopeptides that are able to bind influenza virus multivalently and inhibit adhesion of the virus to cells 10(3)-fold more effectively than a monomeric glycoside of Neu5Acalpha. Another antiviral strategy based on virus-promoted assembly of the glycopeptides was also demonstrated. Consequently, the self-assembly principle offers new perspectives on the design of multivalent antivirals.

Assembly of Oligoglycine Layers on Mica Surface

“…We analyzed conceivable ways of [Gly 7 -NHCH 2 ] 4 C packaging in tectomers and choose the model, in which [Gly 7 -NHCH 2 ] 4 C monomers with paired antennae in polyglycine II conformation are situated normally to the tectomer plane. Thickness of this model structure is in the best agreement to thickness of tectomers measured by scanning force microscopy (SFM), 4.5 nm [6]. Later we showed that tectomers can be formed on a surface more readily than in solution volume, particularly on mica due to the opposite charges of terminal NH 2 groups and mica surface [7].…”

“…Analyzing possible ways of the peptides packing into such crystalline layers we have fixed our attention on the variants presented in Scheme 2. Thus, for the tetraantennary peptide, "2+2" packaging, in which two coplanar pairs of peptide antennae are oppositely directed, seems to be favorable as also is for solution-formed tectomer platelets studied earlier [6]. The triantennary molecule are presumably packed in tectomer layer as a trident ("3+0" packaging).…”

“…Protonated forms of oligoglycines (Scheme 1) are incapable of self assembling due to the charge on the amino group, thus they exist in solution as monomers [6]. To initiate the assembling, an equivalent amount of base is added to aqueous solution of peptide salt.…”

“…Peptides [Gly 7 of the chain by one or two glycine residues [6,9], and stored as HCl or CF 3 COOH salts. SFM images were recorded using a Nanoscope IIIa (Digital Instrument Inc., CA) in air in tapping mode using microcantilevers with a typical resonance frequency 300 kHz and spring constant 42 N/m, and in aqueous solutions in contact mode using The samples for the investigation in air were prepared as followed.…”

“…In polyglycine II structure, parallel peptide chains are arranged as 3 1 helix forming a net of hydrogen bonds (all CO and NH groups are involved) [4][5][6]; this package is rigid and thus especially attractive for design of new flat layers and for smoothening of other rough surfaces. Canonical polyglycine II is formed by a long-chain polymer Gly n in a solid phase [4]; earlier, we have demonstrated that short oligoglycines with n = 7 are capable of forming the polyglycine II architecture if four chains are organized in a star-like manner [6]. Such symmetrical tetraantennary peptide [Gly 7 -NHCH 2 ] 4 C forms platelet-like 2D supramolecular assemblies (hereinafter referred as tectomers), which are proved to be stable not only in solid phase but also in aqueous solutions.…”