1.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.
2.Hydroxyl radical induced by lipid in Maillard reaction model system promotes diet-derived N(ε)-carboxymethyllysine formation.
Han L1, Li L, Li B, Zhao D, Li Y, Xu Z, Liu G. Food Chem Toxicol. 2013 Oct;60:536-41. doi: 10.1016/j.fct.2013.07.081. Epub 2013 Aug 16.
N(ε)-carboxymethyllysine (CML) is commonly found in food, and is considered as a potential hazard to human health. However, the effect of lipids on CML formation in Maillard reaction is still not clarified. In this study, the content of diet-derived CML and its key intermediates, epsilon-fructoselysine (FL) and glyoxal (GO), is determined with high performance liquid chromatography mass spectrum (HPLC-MS) in model system containing lipid compounds. According to the results, hydroxyl radical (OH) induced by Fenton reagent can promote the three pathways of CML formation. Moreover, in the Maillard reaction system, linoleic acid (Lin), oleic acid (Ole) and glycerol trioleate (Tri) can induce more OH·, which promotes CML formation. Their level of promoting CML formation is in the order of Ole>Lin>Tri. On the contrary, glycerol (Gly) can scavenge OH·, which inhibit the CML formation. Finally, it is proved that FL content and GO content decreases with heating time in model system, while CML content increases with heating time.
3.Flow and Microwave-Assisted Synthesis of N-(Triethylene glycol)glycine Oligomers and Their Remarkable Cellular Transporter Activities.
Jong T1, Pérez-López AM1, Johansson EM1, Lilienkampf A1, Bradley M1. Bioconjug Chem. 2015 Aug 19;26(8):1759-65. doi: 10.1021/acs.bioconjchem.5b00307. Epub 2015 Jul 23.
Peptidomimetics, such as oligo-N-alkylglycines (peptoids), are attractive alternatives to traditional cationic cell-penetrating peptides (such as R9) due to their robust proteolytic stability and reduced cellular toxicity. Here, monomeric N-alkylglycines, incorporating amino-functionalized hexyl or triethylene glycol (TEG) side chains, were synthesized via a three-step continuous-flow reaction sequence, giving the monomers N-Fmoc-(6-Boc-aminohexyl)glycine and N-Fmoc-((2-(2-Boc-aminoethoxy)ethoxy)ethyl)glycine in 49% and 41% overall yields, respectively. These were converted into oligomers (5, 7, and 9-mers) using an Fmoc-based solid-phase protocol and evaluated as cellular transporters. Hybrid oligomers, constructed of alternating units of the aminohexyl and amino-TEG monomers, were non-cytotoxic and exhibited remarkable cellular uptake activity compared to the analogous fully TEG or lysine-like compounds.
4.A convenient preparation of N (ε)-methyl-L-lysine derivatives and its application to the synthesis of histone tail peptides.
Chi H1, Islam MS, Nsiama TK, Kato T, Nishino N. Amino Acids. 2014 May;46(5):1305-11. doi: 10.1007/s00726-014-1690-6. Epub 2014 Feb 23.
A convenient route is established for the preparation of N (α)-Fmoc-N (ε)-(Boc, methyl)-L-lysine and N (α)-Fmoc-N (ε)-dimethyl-L-lysine as building blocks to be used for the synthesis of methylated peptides. This methodology is based on the use of malonate derivatives and dibromobutane to produce key intermediates, L-2-amino-6-bromohexanoic acid derivatives, which could be modified to the required group at the ε-position. Fmoc-protection is accessible, so these compounds can be used in solution as well as in solid-phase peptide synthesis. Also the peptides containing these methylated lysines have been proved to resist the action of trypsin and lysyl endopeptidase. Thus, this new method could be considered as an improvement of the synthesis of N (ε)-methyl-L-lysine derivatives.