Self-assembled peptide amphiphiles function as multivalent binder with increased hemagglutinin affinity

Abstract

BackgroundA promising way in diagnostic and therapeutic applications is the development of peptide amphiphiles (PAs). Peptides with a palmitic acid alkylchain were designed and characterized to study the effect of the structure modifications on self-assembling capabilities and the multiple binding capacity to hemagglutinin (HA), the surface protein of influenza virus type A. The peptide amphiphiles consists of a hydrophilic headgroup with a biological functionality of the peptide sequence and a chemically conjugated hydrophobic tail. In solution they self-assemble easily to micelles with a hydrophobic core surrounded by a closely packed peptide-shell.ResultsIn this study the effect of a multiple peptide binding partner to the receptor binding site of HA could be determined with surface plasmon resonance measurements. The applied modification of the peptides causes signal amplification in relationship to the unmodified peptide wherein the high constant specificity persists. The molecular assembly of the peptides was characterized by the determination of critical micelle concentration (CMC) with concentration of 10-5 M and the colloidal size distribution.ConclusionThe modification of the physico-chemical parameters by producing peptide amphiphiles form monomeric structures which enhances the binding affinity and allows a better examination of the interaction with the virus surface protein hemagglutinin.

Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition

“…Thereafter, a peptide was optimized for HA binding by selection from a phage‐displayed random peptide library 24. This work also showed a multivalent improvement of its binding properties by conjugation to either an amphiphilic N ‐stearoyl derivative, which formed self‐assembled multivalent structures with enhanced binding capabilities or by presenting up to six peptide copies on a carbosilane dendrimer 24, 30, 31…”

Applying Multivalent Biomolecular Interactions for Biosensors

“…While the binding constantf or as ingle sialic acid molecule to as ingle HA receptor is relatively weak (K d :1m m), the affinity between viral receptors and cell surface sialic acidsincreases substantially with estimated K d :0 .1 pm. [10] As ynthetically prepared oligomeric PNA-fucose conjugate exhibited as ubnanomolar affinity against ap athogenic lectin protein, representing more than a 1000-fold increase from af ucose monomer. [11] This oligomeric fucose inhibited pathogenic bacterium infection on epithelial cells over700-fold more effectively than monomeric fucose.…”

Development of a hybrid peptide dendrimer micellar carrier system and its application in the reformulation of a hydrophobic therapeutic agent derived from traditional Chinese medicine

“…Hydrophobic core (decanoic acid) and hydrophilic branching resulted in surfactant like behaviour of lipidated dendrimers tend to self-assemble into micelles in diluted aqueous solution. 19 The amphiphilic nature of lipidated dendrimers (monomers) at certain concentration or at critical micelle concentration (CMC) aggregate to form micelles as shown in the Fig. 4.…”