phenyldehydroalanine and 2-aminoisobutyric-acid

Peptide-based capping agents for gold nanoparticles (GNPs) are possible alternatives for capping and derivatizing GNPs, but suffer from a major disadvantage of sensitivity toward non specific proteases, which may limit their in vivo utility. Using non-natural analogs of natural α-amino acids offer an attractive alternate strategy to circumvent this potential bottleneck in realizing full potential of peptide based capping gents for GNPs for biological applications. Here, we have designed and developed pentapeptides containing non-natural amino acid (α,β-dehydrophenylalanine and α-aminoisobutyric acid) as capping agents for GNPs. All these peptides were able to efficiently cap GNPs and peptide induced aggregation was not observed. Peptide capped GNPs showed minimal cytotoxicity to mammalian cell lines (HeLa and L929) as well as mice spleenocytes. They encapsulated small drug like molecules and peptide capped GNPs entrapping drugs were more efficient in killing HeLa cells compared to the free drug. Therefore, these non-natural amino acid containing peptide-capped GNPs may be further developed as alternate drug delivery vehicles.

Topics: Aminoisobutyric Acids; Animals; Antimalarials; Antineoplastic Agents; Cell Line; Cell Survival; Chloroquine; Doxorubicin; Drug Carriers; Drug Delivery Systems; Gold; HeLa Cells; Humans; Metal Nanoparticles; Mice; Peptides; Phenylalanine

A new optically inactive 3(10)-helical peptide with a side-chain cross-linking was found to exhibit chiral memory stored in the peptide backbone, whose chirality was induced by a noncovalent interaction of a chiral molecule at the N-terminal end of the peptide.

Topics: Aminoisobutyric Acids; Circular Dichroism; Kinetics; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides; Phenylalanine; Piperidines; Protein Structure, Secondary; Stereoisomerism

Recently, a novel chiral intermolecular interaction was found in an N-deprotected achiral nonapeptide that undergoes the predominance of one-handed screw sense through the addition of chiral small carboxylic acid (Inai, Y.; Tagawa, K.; Takasu, A.; Hirabayashi, T.; Oshikawa, T.; Yamashita, M. J. Am. Chem. Soc. 2000, 122, 11731). We here clarify to what extent such noncovalent chiral domino effect affects the helical screw sense of an N-deprotected chiral peptide. Two chiral peptides consisting of C-terminal L-Leu (1) or L-Leu(2) (2) and the preceding achiral helical octapeptide segment were employed. NMR and IR spectroscopy, and energy calculation indicated that both peptides adopt a helical conformation in chloroform. Peptide 1 showed a small excess of a left-handed screw sense for the achiral helical octapeptide, but peptide 2 strongly preferred a right-handed screw sense. The addition of chiral Boc amino acid to a chloroform solution of peptide 1, depending on its chirality, underwent a unique helix-to-helix transition or led to remarkable stabilization of the original left-handed screw sense. Peptide 2 retained the original right-handed screw sense on addition of chiral Boc-amino acid, but its helical stability changed to some extent depending on its added chirality. Therefore, the importance of noncovalent domino effect for controlling the helical screw sense or helical stability of a chiral peptide has been demonstrated here for the first time. In addition, we here have presented a unique system that both N-terminal noncovalent and C-terminal covalent domino effects operate simultaneously on the helical screw sense of a single achiral segment and have compared both powers for inducing the screw sense bias.

Topics: Aminoisobutyric Acids; Circular Dichroism; Models, Molecular; Oligopeptides; Phenylalanine; Protein Structure, Secondary