3182-85-2Relevant academic research and scientific papers
Effect of double replacement of L-Pro, D-Pro, D-Leu or Nleu in hydrophobic face of amphipathic α-helical model antimicrobial peptide on structure, cell selectivity and mechanism of action
Shin, Song Yub
, p. 3267 - 3274 (2015/04/22)
In order to investigate the effects of the double replacement of L-Pro, D-Pro, D-Leu or Nleu (the peptoid residue for Leu) in the hydrophobic face (positions 9 and 13) of amphipathic α-helical non-cell-selective antimicrobial peptide L8K9W1 on the structure, cell selectivity and mechanism of action, we synthesized a series of L8K9W1analogs with double replacement of L-Pro, D-Pro, D-Leu or Nleu in the hydrophobic face of L8K9W1. In this study, we have confirmed that the double replacement of L-Pro, D-Pro, or Nleu in the hydrophobic face of L8K9W1 let to a great increase in the selectivity toward bacterial cells and a complete destruction of α-helical structure. Interestingly, L8K9W1-L-Pro, L8K9W1-D-Pro and L8K9W1-Nleu preferentially interacted with negatively charged phospholipids, but unlike L8K9W1 and L8K9W1-D-Leu, they did not disrupt the integrity of lipid bilayers and depolarize the bacterial cytoplasmic membrane. These results suggested that the mode of action of L8K9W1-L-Pro, L8K9W1-D-Pro and L8K9W1-Nleu involves the intracellular target other than the bacterial membrane. In particular, L8K9W1-L-Pro, L8K9W1-D-Pro and L8K9W1-Nleu had powerful antimicrobial activity (MIC range, 1 to 4 μM) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Taken together, our results suggested that L8K9W1-L-Pro, L8K9W1-D-Pro and L8K9W1-Nleu with great cell selectivity may be promising candidates for novel therapeutic agents, complementing conventional antibiotic therapies to combat pathogenic microorganisms.
Self-assembled nanostructures of long-acting GnRH analogs modified at position 7
Zhou, Ning,Lv, Yujian,Cheng, Junping,Zhou, Wenxia,Liu, Keliang,Gao, Xing
, p. 868 - 875 (2015/12/05)
It is well known that GnRH analogs can self-assemble into amyloid fibrils and that the duration of action of GnRH analogs depends on the ability of the amyloid to slowly release active peptides. The aim of this study was to investigate the influence of the amino acid residues at position 7 of GnRH analogues on peptide self-assembly. It was found that the dominant shape of the nanostructure can be changed when the structures of the residues at position 7 differ significantly from that of leucine in Degarelix. When the backbone length was extended (peptide 9), or the side chain of the residue at position 7 was replaced by an aromatic ring (peptide 6), or the rotation of the amide bond was restricted (peptide 8), the nanostructure changed from fibrils to vesicles. The results also indicate that the increasing hydrophilicity had little influence on the nanostructure morphology. In addition, a suitable release rate was found to play a more important role for the duration of the peptide action by maintaining the equilibrium between the drug concentration and the persistent release time, while the nanostructure shape was found to exert little influence on the duration of the peptide action.
Rearrangement of Azidomalonic Esters
Frank, Juergen,Stoll, Gerhard,Musso, Hans
, p. 1990 - 1996 (2007/10/02)
Dimethyl azidomalonate (4) is photolyzed under loss of nitrogen and rearrangement of one methoxycarbonyl group to form the mixture of Z and E isomers of the α,β-unsaturated amino acid esters 8 and 9.On photolysis of isopropyl- and isobutylazidomalonates 10 migration of the alkyl group is observed exclusively.The (alkylimino)malonates 14 so formed have been hydrogenated and hydrolyzed to give the N-alkylglycine derivatives 16.
