Hydrogen Bonding in a l-Glutamine-Based Polyamidoamino Acid and its pH-Dependent Self-Ordered Coil Conformation

Abstract

This paper reports on synthesis, acid–base properties, and self-structuring in water of a chiral polyamidoamino acid, M-l-Gln, obtained from the polyaddition of N,N′-methylenebisacrylamide with l-glutamine, with the potential of establishing hydrogen bonds through its prim-amide pendants. The M-l-Gln showed pH-responsive circular dichroism spectra, revealing ordered conformations. Structuring was nearly insensitive to ionic strength but sensitive to denaturing agents. The NMR diffusion studies were consistent with a population of unimolecular nanoparticles thus excluding aggregation. The M-l-Gln had the highest molecular weight and hydrodynamic radius among all polyamidoamino acids described. Possibly, transient hydrogen bonds between l-glutamine molecules and M-l-Gln growing chains facilitated the polyaddition reaction. Theoretical modeling showed that M-l-Gln assumed pH-dependent self-ordered coil conformations with main chain transoid arrangements reminiscent of the protein hairpin motif owing to intramolecular dipole moments and hydrogen bonds. The latter were most numerous at the isoelectric point (pH 4.5), where they mainly involved even topologically distant main chain amide N–H and side chain amide C=O brought to proximity by structuring. Hydrogen bonds at pH 4.5 were also suggested by variable temperature NMR. The 2D NOESY experiments at pH 4.5 confirmed the formation of compact structures through the analysis of the main chain/side chain hydrogen contacts, in line with MD simulations.

Adsorption and Self-Aggregation of Chiral [5]-Aza[6]helicenes on DNA Architecture: A Molecular Dynamics Study

“…For about 25 years, personal attention has been paid to atomistic simulations based on MM and MD methods. The possibility of understanding the role of noncovalent intermolecular interactions is interesting, for example, in the adsorption process of proteins on biomaterial surfaces; − in the chiral discrimination in host–guest compounds involving cyclodextrins; and in the nanoaggregation process of carriers and drugs for drug delivery. − These theoretical studies can be useful in explaining experimental data from circular dichroism and two-dimensional NMR spectra when the experimental data are accessible. In some cases, these studies may also be useful in predicting the unfolding state and denaturation of albumin on ordered graphite surfaces, − the solubilization of carbon nanotubes using proteins − or indicating the discrimination of chiral molecules using chiral NTs …”

Vibrational Properties of (8,8) and (10,10) SWCNTs before and after Albumin Fragment Adsorption: A Molecular Dynamics Study

“…Molecular modeling and computer simulations can yield significant new insight at the atomistic level about the bulk and surface properties materials. [13][14][15] In the past, 20 years Molecular Mechanics (MM) and Molecular Dynamics (MD) simulations have demonstrated to be a very useful tool to describe at atomistic level the conformational properties of drugs [16,17] and polymers, [18,19] and the protein adsorption process on biomaterial surfaces. [20,21] About the protein adsorption on graphite and on SWNTs, the role of the curvature of different nanotubes and possible chiral discrimination after the inclusion in the inner cavity [22,23] are particularly important.…”

Highlight on the Mechanism of Linear Polyamidoamine Degradation in Water

“…Linear polyamidoamines (PAAs) are the aza-Michael polyaddition products of prim-monoamines or bis-sec-amines with bisacrylamides [ 1 , 2 , 3 ]. A recent development of PAA chemistry consisting of employing natural α-amino acids as monomers has led to polyamidoamino acids (PAACs), a novel class of polymers deriving from natural α-amino acids, which maintain the α-amino acid chirality and amphoteric properties [ 4 , 5 , 6 , 7 , 8 , 9 ]. The controlled synthesis of PAACs has recently been reported [ 10 ].…”