Enantioselective Binding and Stable Encapsulation of α-Amino Acids in a Helical Poly(L-glutamic acid)-Shelled Dendrimer in Aqueous Solutions

Abstract

A novel water-soluble peptide-shelled dendrimer containing a poly(L-glutamic acid) segment grafted on the third-generation poly(amido amine) dendrimer was successfully synthesized, and its secondary structural properties and interaction with alpha-amino acids (Trp, Phe, and Tyr) were revealed by spectroscopic measurements. In the lower pH region, this peptide-dendrimer adopted an alpha-helix conformation with almost 100 % helicity resulting from the three-dimensional aggregation of the segment. Interactions with alpha-amino acids proceeded with positive cooperativity on the basis of a Hill plot, and as a result, D isomers preferentially bound to the alpha-helical segments relative to L isomers. The bound alpha-amino acids were not released into the water phase but were transferred into the inner core of the dendrimer where they remained stable, even when a conformational change of the helix segment was caused by pH variation.

Dendrimer-protein interactions versus dendrimer-based nanomedicine

“…To understand the basics of dendrimer-protein interactions, Higashi et al [20] synthesized a peptide-shelled dendrimer containing a poly(l-glutamic acid) segment grafted on the 3rdgeneration PAMAM dendrimer and analyzed its interaction with hydrophobic ␣-amino acids (Trp, Phe, and Tyr). This dendrimer bound to ␣-amino acids with positive cooperativity on the basis of a Hill plot; as a result, d-isomers preferentially bound to the ␣-helical segments relative to l-isomers [20]. Using electron paramagnetic resonance, Ottaviani et al [21] studied the interaction between cationic PAMAM-NH 2 dendrimers of 2nd (g2) and 6th (g6) generations, amino acids (Gly, Glu, Arg, Leu) and proteins (␣chymotrypsin, albumin).…”

Preparation of helical peptide monolayer-coated gold nanoparticles

“…Dendrimers have also attracted increasing interest as templates and cores for designing nanoparticles. We have prepared peptide dendrimers, in which polypeptide segments are linked covalently with the peripheries of a polyamidoamine dendrimer [9][10][11]. Peptide segments of the dendrimers exhibited unique properties in solutions such as enhancement in helicity [9] and enantiomeric binding of amino acids [10] due to assembled structure of helices, different from that in bulk.…”

Effect of Terminal-Group Functionality on the Ability of Dendrimers to Bind Proteins

“…Hamilton later showed how a series of functionalized porphyrins with different groups could bind to a series of proteins with high affinity. 20 In addition to our results using dendrimers, Higashi 21 showed how dendrimers terminated with poly-glutamic acid could be used to bind amino acids (as opposed to proteins). The glutamic ends formed -helices, which preferentially bound D-amino acids with positive cooperativity.…”