Monitoring surface functionalization of dendrigraft poly-L-lysines via click chemistry by capillary electrophoresis and Taylor dispersion analysis.

Click chemistry by copper-mediated azide/alkyne cycloaddition reaction is known as a very efficient synthetic pathway for chemical coupling and for surface functionalization. The attractiveness of this reaction is due to the selectivity of the reaction of azides and alkynes. Nevertheless, the control of the kinetics of the reaction and the characterization of the reaction products requires the use of adequate analytical techniques.

Dendrigraft poly-L-lysine: a non-immunogenic synthetic carrier for antibody production.

An easily synthesized DendriGraft poly-lysine DGL-G3 (third generation) was shown to act as an efficient carrier for raising antibodies directed against small molecules. The immunological properties of three different forms of DGL-G3 were investigated: the native form (molecular weight 22 kDa bearing a mean number of 123 surface amino groups as TFA salts), a form modified at the C-terminus by fluorescein (fluorescein-DGL-G3), and last a surface-modified form bearing histamine (DGL-G3-Histamine). Our studies demonstrate the native DGL-G3 to be inefficient in eliciting antibody production in rabbits.

An expeditious multigram-scale synthesis of lysine dendrigraft (DGL) polymers by aqueous N-carboxyanhydride polycondensation.

The synthesis and characterisation of new arborescent architectures of poly(L-lysine), called lysine dendrigraft (DGL) polymers, are described. DGL polymers were prepared through a multiple-generation scheme (up to generation 5) in a weakly acidic aqueous medium by polycondensing N(epsilon)-trifluoroacetyl-L-lysine-N-carboxyanhydride (Lys(Tfa)-NCA) onto the previous generation G(n-1) of DGL, which was used as a macroinitiator. The first generation employed spontaneous NCA polycondensation in water without a macroinitiator; this afforded low-molecular-weight, linear poly(L-lysine) G1 with a polymerisation degree of 8 and a polydispersity index of 1.

Poly(L-proline) II helix propensities in poly(L-lysine) dendrigraft generations from vibrational Raman optical activity.

Vibrational Raman optical activity (ROA), measured as small circularly polarized components in Raman scattering from chiral molecules, was applied to study the backbone conformations of the first five generations of poly(L-lysine) dendrigrafts (DGLs) in water. Generation 1 was found to support predominantly the poly(L-proline) II (PPII) conformation, the amount of which steadily decreased with increasing generation, with a concomitant increase in other backbone conformations. This behavior may be due to increasing crowding of the lysine side chains, together with suppression of backbone hydration, with increasing branching.

Interaction and transport of poly(L-lysine) dendrigrafts through liposomal and cellular membranes: the role of generation and surface functionalization.

Two generations of poly(l-lysine) dendrigrafts (DGLs) were studied with regard to their ability to interact with and translocate through liposomal and cellular membranes. Partial guanidinylation of the surface amino groups of the starting dendrigrafts afforded the guanidinylated derivatives whose membrane translocation properties were also assessed. Mixed liposomes, consisting of dihexadecyl phosphate, phosphatidylcholine, and cholesterol, were employed as model membranes, while A549 human lung carcinoma cells were used for cellular uptake studies.

Determination of dendrigraft poly-L-lysine diffusion coefficients by taylor dispersion analysis.

This work focuses on the physicochemical characterization of dendrigraft poly-L-lysines (DGLs) obtained by polymerization of N-carboxyanhydride in buffered water (pH 6.5). Diffusion coefficients (D) and hydrodynamic radii (Rh) of five successive DGL generations were determined by Taylor dispersion analysis (TDA).

Emergence of homochirality in far-from-equilibrium systems: mechanisms and role in prebiotic chemistry.

Since the model proposed by Frank (Frank FC, Biochem Biophys Acta 1953;11:459-463), several alternative models have been developed to explain how an asymmetric non-racemic steady state can be reached by a chirally symmetric chemical reactive system. This paper explains how a stable non-racemic regime can be obtained as a symmetry breaking occurring in a far-from-equilibrium reactive system initiated with an initial imbalance. Departing from the variations around the original Frank's model that are commonly described in the literature, i.

Recycling Frank: Spontaneous emergence of homochirality in noncatalytic systems.

In this work, we introduce a prebiotically relevant protometabolic pattern corresponding to an engine of deracemization by using an external energy source. The spontaneous formation of a nonracemic mixture of chiral compounds can be observed in out-of-equilibrium systems via a symmetry-breaking phenomenon. This observation is possible thanks to chirally selective autocatalytic reactions (Frank's model) [Frank, F.

Dynamic co-evolution of peptides and chemical energetics, a gateway to the emergence of homochirality and the catalytic activity of peptides.

We propose a scenario for the dynamic co-evolution of peptides and energy on the primitive Earth. From a multi component system consisting of hydrogen cyanide, several carbonyl compounds, ammonia, alkyl amine, carbonic anhydride, borate and isocyanic acid, we show that the reversibility of this system leads to several intermediate nitriles, that irreversibly evolve to alpha-amino acids and N-carbamoyl amino acids via selective catalytic processes. On the primitive Earth these N-carbamoyl amino acids combined with energetic molecules (NOx) may have been the core of a molecular engine producing peptides permanently and assuring their recycling and evolution.