1.Modulation of neutrophil phospholipase C activity and cyclic AMP levels by fMLP-OMe analogues.
Ferretti ME1, Nalli M, Biondi C, Colamussi ML, Pavan B, Traniello S, Spisani S. Cell Signal. 2001 Apr;13(4):233-40.
The N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-OMe (1) analogues for-Thp-Leu-Ain-OMe (2), for-Thp-Leu-Phe-OMe (3), for-Met-Leu-Ain-OMe (4), for-Met-Delta(z)Leu-Phe-OMe (5), for-Met-Lys-Phe-For-Met-Lys-Phe (6), for-Met-Leu-Pheol-COMe (7), and for-Nle-Leu-Phe-OMe (8) have been studied. Some of these have been found selective towards the activation of different biological responses of human neutrophils. In particular, peptides 2 and 3, which evoke only chemotaxis, are ineffective in enhancing inositol phosphate, as well as cyclic AMP (cAMP) levels. On the contrary, analogues 5 and 7, which induce superoxide anion production and degranulation, but not chemotaxis, significantly increase the levels of the two intracellular messengers, as is the case of the full agonists 1 and 6. The Ca(2+) ionophore A23187 also activates phospholipase C (PLC) and increases the nucleotide levels; when tested in combination with peptide 1 or 5, a supra-additive enhancement of cAMP concentration is obtained.
2.Sonication-induced coiled fibrous architectures of Boc-L-Phe-L-Lys(Z)-OMe.
Afrasiabi R1, Kraatz HB. Chemistry. 2013 Jan 28;19(5):1769-77. doi: 10.1002/chem.201202268. Epub 2012 Dec 19.
An ultra-short peptide Boc-L-Phe-L-Lys(Z)-OMe (Z=carbobenzyloxy) was shown to act as a highly efficient and versatile low molecular weight gelator (LMWG) for a variety of aliphatic and aromatic solvents under sonication. Remarkably, this simple dipeptide is not only able to form coiled fibres but also demonstrates self-healing and thermal chiroptical switching behaviour. The formation of coiled assemblies was found to be influenced by the nature of the solvent and the presence of an additive. By exploiting these properties it was possible to modulate the macroscopic and microscopic properties of the organogels of this ultra-short peptide, allowing the formation of highly ordered single-domain networks of helical fibres with dimeric or alternatively fibre-bundle morphology. The organogels were characterized by using FTIR, SEM, NMR and circular dichroism (CD) spectroscopy. Interestingly, CD experiments showed that the organogels of Boc-L-Phe-L-Lys(Z)-OMe in aromatic solvents exhibit thermal chiroptical switching.
3.Radical acylation of L-lysine derivatives and L-lysine-containing peptides by peroxynitrite-treated diacetyl and methylglyoxal.
Tokikawa R1, Loffredo C, Uemi M, Machini MT, Bechara EJ. Free Radic Res. 2014 Mar;48(3):357-70. doi: 10.3109/10715762.2013.871386. Epub 2014 Jan 7.
Highly electrophilic α-dicarbonyls such as diacetyl, methylglyoxal, 3-deoxyglucosone, and4,5-dioxovaleric acid have been characterized as secondary catabolites that can aggregate proteins and form DNA nucleobase adducts in several human maladies, including Alzheimer's disease, rheumatoid arthritis, diabetes, sepsis, renal failure, and respiratory distress syndrome. In vitro, diacetyl and methylglyoxal have also been shown to rapidly add up the peroxynitrite anion (k2 ~ 10(4)-10(5) M(-1) s(-1)), a potent biological nucleophile, oxidant and nitrosating agent, followed by carbon chain cleavage to carboxylic acids via acetyl radical intermediate that can modify amino acids. In this study, we used the amino acid derivatives Ac-Lys-OMe and Z-Lys-OMe and synthesized the tetrapeptides H-KALA-OH, Ac-KALA-OH, and H-K(Boc)ALA-OH to reveal the preferential Lys amino group targeted by acyl radical generated by the α-dicarbonyl/peroxynitrite system. The pH profiles of the reactions are bell-shaped, peaking at approximately 7.