Self-Ordering Secondary Structure of d- and l-Arginine-Derived Polyamidoamino Acids

Abstract

This paper reports on synthesis, acid–base properties and pH-dependent structuring in water of d-, l- and d,l-ARGO7, bioinspired polymers obtained by polyaddition of the corresponding arginine stereoisomers with N,N′-methylenebis(acrylamide). The circular dichroism spectra of d- and l-ARGO7 showed a peak at 228 nm and quickly and reversibly responded to pH changes, but were nearly unaffected by temperature, ionic strength, and denaturating agents. Theoretical modeling studies of L-ARGO7 showed that it assumed a folded structure. Intramolecular interactions led to transoid arrangements of the main chain reminiscent of the protein hairpin motif. Torsion angles showed a quite similar distribution at pH 6 and 14 consistent with the similarity of the CD spectra from pH 6 upward

pH-Dependent Chiral Recognition of D- and L-Arginine Derived Polyamidoamino Acids by Self-Assembled Sodium Deoxycholate

“…When the NaDC/D-ARGO7 ratio ≤1, that is at 35 and 70 mg mL −1 of D-ARGO7 and 35 mg mL −1 NaDC, the addition of the polymer neutralized some of NaDC carboxylate groups and the object that is now causing scattering is composed of ellipsoidal NaDC and spherical ARGO7, in close proximity, due to the electrostatic interactions and the formation of hydrogen bonding (Figure 4a). The shape of the polymer and its surface charge are known from previous work [24,25]. In conclusion, when NaDC/D-ARGO7 ratio ≤ 1, SANS data confirmed the existence of electrostatic interactions between NaDC and D-ARGO7 in the liquid phase.…”

“…D-, L, and D,L-ARGO7 were prepared in water by the Michael-type polyaddition of D-, Lor D,L-arginine with equimolar quantities of N,N'-methylenebisacrylamide (MBA) (Scheme 1), following a previously described procedure [25] here recalled in Materials and Methods. The weight-average molecular weights (M w ) of all three stereoisomers were comparable.…”

“…Land D-ARGO7, the latter prepared from D-arginine, exhibited pH-dependent circular dichroism (CD) spectra suggesting the existence of pH-sensitive conformations [25]. Molecular dynamic studies on L-ARGO7 shed light on these conformations, whose relevant characteristic was the similarity with the "hairpin" motif of proteins [25]. This characteristic was shared by other PAACs prepared from L-alanine, L-valine, L-leucine [26].…”

“…A different class of stimuli responsive polymers based on α-amino acids, named polyamidoamino acids (PAACs), has been obtained by the Michael-type polyaddition of α-amino acids with bisacrylamides, as for instance N,N'-methylenebisacrylamide [24][25][26][27][28][29][30], 2,2'-bis(acrylamidoacetic) acid [29][30][31], and 1,4-bis(acryloyl)piperazine [32]. In particular, the PAAC named L-ARGO7 was obtained from N,N'-methylenebisacrylamide and L-arginine [24].…”

“…L-ARGO7 proved highly cytobiocompatible (IC 50 ≥ 8 mg mL −1 ) and was easily internalized in Balb/3T3 cells. Land D-ARGO7, the latter prepared from D-arginine, exhibited pH-dependent circular dichroism (CD) spectra suggesting the existence of pH-sensitive conformations [25]. Molecular dynamic studies on L-ARGO7 shed light on these conformations, whose relevant characteristic was the similarity with the "hairpin" motif of proteins [25].…”