10.1016/j.tet.2005.05.021
The research focuses on the efficient synthesis of (S)-homolysine and (S)-bishomoarginine, which are analogues of the cationic amino acids lysine and arginine, respectively. These homologues are valuable in drug discovery, particularly in the development of peptidic enzyme inhibitors and for probing enzyme active sites. The synthesis strategy avoids the use of chiral templates by incorporating commercially available (S)-allylglycine and utilizes olefin cross-metathesis for chain elongation. The synthesis of (S)-homolysine involves five steps with an overall yield of 55%, which is an improvement over previous methods. (S)-Bishomoarginine is prepared in six steps with a 57% overall yield. Key reactants include bromobutene, di-tert-butyliminodicarboxylate, cesium carbonate, and Grubbs’ ruthenium catalyst, among others. The synthesis involves protection and deprotection steps, cross-metathesis reactions, and hydrogenation. Analyses used to confirm the structure and purity of the compounds include NMR spectroscopy, specific rotation measurements, and chiral GC analysis.
10.1002/cbic.201000759
The research presents an in-depth study on the transport of free and peptide-bound glycated amino acids, focusing on their synthesis, transepithelial flux across Caco-2 cell monolayers, and interactions with apical membrane transport proteins. The experiments involved the synthesis of various glycated amino acids and dipeptides through non-enzymatic chemical processes known as the Maillard reaction, using reactants like lysine, arginine, glucose, and other sugars. The synthesized products were analyzed using techniques such as high-pressure liquid chromatography (HPLC), amino acid analysis (AAA), nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and elemental analysis. The study also measured the inhibition of lysine and glycylsarcosine uptakes in Caco-2 cells, which express transporters like PEPT1 and lysine transport systems, to understand the affinities and transport characteristics of these glycated compounds. The results provided insights into the intestinal absorption mechanisms of dietary Maillard reaction products and their potential impact on human health.
10.1021/ja0587603
The research presents an in-depth study on the biosynthesis of pipecolic acid by RapL, a lysine cyclodeaminase enzyme encoded in the rapamycin gene cluster. The main focus of the study is to validate RapL's ability to convert L-lysine to L-pipecolic acid through a cyclodeamination reaction involving redox catalysis. The researchers heterologously overexpressed and purified RapL, and conducted a series of experiments to confirm its enzymatic activity. They used L-lysine and L-[U-14C]ornithine as substrates, NAD+ as a cofactor, and analyzed the reactions using techniques such as cellulose thin layer chromatography (TLC), chiral radio-HPLC, and mass spectrometry. The study also investigated the enzyme's substrate specificity, cofactor requirements, and inhibitory properties. Additionally, the researchers used isotopically labeled substrates to dissect the mechanistic details of the cyclodeaminase reaction, confirming the loss of the R-amine and retention of the hydrogen atom at the R-carbon. The experiments provided the first in vitro characterization of a lysine cyclodeaminase and contributed to the understanding of the biosynthesis of medically important natural products like rapamycin, FK506, and FK520.
10.1039/c2jm16598h
The study presents the synthesis and application of a novel molecule, lysine-dopamine (LDA), which was inspired by the adhesive properties of mussels and the bio-functionality of L-lysine. LDA serves as a universal modifier for various surfaces to enhance their biocompatibility, cell adhesion, and promote cell growth. The chemicals used in the study include L-lysine, N-hydroxysuccinimide (NHS), di-t-butyl dicarbonate ((Boc)2O), dopamine hydrochloride (DA-HCl), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl) for the synthesis of LDA. These chemicals were utilized in a series of reactions to create LDA, which was then applied to different substrates through a simple dip-coating process. The purpose of these chemicals was to create a functional molecule that could mimic the strong adhesion properties of mussel proteins and improve the biocompatibility of surfaces for biomedical applications.
10.1055/s-0028-1088208
The research explores the application of the Sonogashira reaction to couple alkenyl chlorides with aliphatic acetylenes, aiming to develop a method for synthesizing enediynes from amino acid derivatives. This approach is significant as it offers an alternative to the more expensive and unstable vinyliodides commonly used in natural product synthesis. The study found that using piperidine as a base and optimizing reaction conditions were crucial for successful coupling, especially with less reactive alkenyl chlorides. The researchers synthesized various enediyne-bridged peptide motifs using amino acids like glycine, alanine, valine, phenylalanine, tyrosine, and lysine, achieving yields ranging from 30% to 77%. The results demonstrate the potential of the Sonogashira reaction for synthesizing complex natural products and highlight its applicability in creating enediyne structures with promising biological activities, such as DNA cleavage and antimicrobial properties.
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