Stereoselectivity Aspects in the Condensation of Racemic NCA−Amino Acids in the Presence and Absence of Liposomes

Abstract

In previous work dealing with the liposome-assisted polycondensation of NCA (N-carboxyanhydride)−amino acids, it has been shown that racemic NCA−Trp condensation affords chains with preferential homochiral sequences: the homochiral blocks become increasingly over-represented with increasing oligomer length if compared with the statistically (Bernoullian) distributions. The present paper deals with three questions related to this stereoselective NCA−Trp condensation. The first question concerns the kinetic mechanism that is responsible for the over-representation of homochiral sequences in the presence as well as in the absence of liposomes. To this aim, we have investigated whether and to what extent the selection of the entering chiral monomer unit is governed by the chirality of the penultimate residue. This analysis allows one to suggest that the polycondensation corresponds to a second- or higher-order Markov process. The second question considered in this paper is whether the preferential formation of homochiral sequences, originally found in NCA−Trp−amino acid condensations, is observed also for amino acids other than Trp as well as for mixtures of different amino acids. To clarify this point, we have analyzed by liquid chromatography mass spectrometry (LC-MS) the condensation products of racemic NCA−d-Leu/perdeuterated NCA−l-Leu and racemic NCA−d-Ile/perdeuterated NCA−l-Ile in an aqueous solution without liposomes. This analysis permits us to show that the preferential homochiral growth occurs also with Leu and Ile. By LC-MS analysis we can show that under the same conditions also mixtures of equal amounts of the l- and d-forms of different amino acids, such as Trp/Leu, Leu/Ile, and Trp/Leu/Ile, exhibit similar behavior. The third question considered in this paper is related to the effect of liposomes on the NCA−Trp condensation, addressing the question of whether the chemical structure of the lipid in the liposomes and consequently their physical state have an influence on the stereoselectivity of the NCA−Trp condensation. To this aim, experiments are carried out at different temperatures in the presence of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine) liposomes, below as well as above the liquid-analogue/crystalline-analogue transition temperature. The answer to the third question is that basically the same results are obtained independently of the physical state of the lipid.