Self-assembling peptide nanotubes from enantiomeric pairs of cyclic peptides with alternating D and L amino acid residues

Cyclic peptides with alternating d- and l-amino acid residues containing tert-leucine residues in every second position can form peptide nanotubes only when both enantiomers of the peptide are present in the solution. These results strongly indicate the formation of peptide nanotubes that assemble with one enantiomer in every second position, thereby forming a lamellar structure.</p

Pharmacodynamic synergy strictly dependent on the co-operative aggregation of enantiomers of cyclic peptides in the bacterial cell membrane

The antimicrobial activity of the peptide enantiomers cyclo[d-Tle-d-Lys-d-Tle-l-Ala-d-Tle-l-Ala-d-Tle-l-Ala] and cyclo[l-Tle-l-Lys-l-Tle-d-Ala-l-Tle-d-Ala-l-Tle-d-Ala] against Bacillus megaterium was investigated. Both these peptides showed very low activity in both an agar diffusion assay and a broth microdilution assay. However, when both peptides were present during the experiments a potent inhibition with an IC(50) value of 2μM was observed. Furthermore, the peptides also showed low hemolytic activity. Neither peptide had any hemolytic activity in concentrations up to 1mM but when erythrocytes were exposed to both peptides a weak hemolytic activity could be observed with a HC(50) value of 316μM.</p

Self-Assembling Peptide Nanotubes from Enantiomeric Pairs of Cyclic Peptides with Alternating d and l Amino Acid Residues

Cyclic peptides with alternating d- and l-amino acid residues containing tert-leucine residues in every second position can form peptide nanotubes only when both enantiomers of the peptide are present in the solution. These results strongly indicate the formation of peptide nanotubes that assemble with one enantiomer in every second position, thereby forming a lamellar structure

Tumour Targeting with Rationally Modified Cell-Penetrating Peptides

Cell-penetrating peptides (CPPs) are short transport peptides with a well-established ability for delivery of bioactive cargoes inside the cells both, in vitro and in vivo. CPPs enter unselectively in a wide variety of cell lines, this is a desirable property for most in vitro applications, however, in vivo e.g. in tumor models, specific targeted accumulation is required. In order to achieve tumor targeting, a known CPP, YTA4, was modified by prolonging it C-terminally with mainly negatively charged amino acids. Additionally, a matrix metalloproteinase-2 cleavage site was introduced between the CPP and the inactivating sequence. This new peptide, named NoPe, is an inactive pro-form of YTA4. It can be selectively cleaved and thereby activated by MMPs. We have conjugated an imaging agent, fluoresceinyl carboxylic acid, and a cytostatic agent methotrexate, to this activable pro-form. NoPe activation was demonstrated in vitro by recombinant MMP-2 cleavage and the cleavage of the attenuating sequence was abolished with MMP-2 specific inhibitor. Furthermore, the fluoresceinyl-NoPe is selectively accumulated in the tumor tissue in MDA-MB-231 tumor bearing mice after intravenous injection. Thus, this strategy proves to be successful for in vivo tumor imaging.</p

Supplementary Figure 2 from Novel Target for Peptide-Based Imaging and Treatment of Brain Tumors

PDF - 8691K, MDGI expression in glioma xenografts.</p