Self-Assembling D,L-Oligonorleucine for Delivery of Bioactive Molecules.

D,L-alternating oligonorleucines are a class of self-assembling peptides that are organized in a ?-sheet motif, resulting in a nano-fibrous architecture. The members with n >= 8 are insoluble even in organic solvents. Upon slight warming, in chlorophorm solution these D,L-oligonorleucines forms gel. Interestingly, if CDCl3 is used, 2H NMR spectra of these gels show a splitting (?6 Hz) of the solvent signal. It appears therefore that the decrease of the solubility in chlorophorm upon increasing n is mainly due to an increasing tendency of the oligomers to self-assembling through intermolecular H bonds. We postulate that interdigitation of the n.butyl of the norleucine residues, mediated from solvent molecule is the determining factor for gel formation. Nle/Leu oligopeptides. A leucine residue in central position of the backbone interrupt the interdigitation of the n.butyl of the norleucine residues that is a determining factor for the stacking. The deca-D,L-oligonorleucine is soluble in organic solvents. 1H-NMR spectra exhibit features, such as low field (>7.2ppm) position of amide NH signals, and the high values (7-10Hz) of the coupling constants 3JNH-CH, that are characteristics of an antiparallel double-stranded structure. The analysis of the TOCSY and ROESY spectra allowed to assign all NH and ?H for sequential assignment. In addition long range connectivities were founds which are compatible with the existence of a dimer in solution. Furthermore some weak connectivities are found that are compatible with a partial superimposition of a thirty strand.