Amino Acids

The enrichment of targeted low-abundance proteins is possible by affinity adsorption using selected sorbents. Different categories of very dilute proteins are present in most of biological extracts so that specific affinity methods are unable to address their collective enrichment. Only recently an interesting approach has been proposed associating the affinity of multiple ligands used as a library mode under overloading much beyond the saturation of the affinity mixed bed. The principle and the limits of this technology are reported along with their current and potential applications in various domains.

The ethynylglycine synthon {(R)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-ethynyl-oxazolidine} is a chiral compound with valuable synthetic interest. An update (covering literature from 2005 to 2017) on the different synthetic utilities is reviewed and discussed.

In the human body, the skin is one of the organs most affected by the aging process. Nutritional approaches aimed to counteract the age-induced decline of extracellular matrix (ECM) deposition could be a valuable tool to decrease the degenerative processes underlying skin aging. Here, we investigated the ability of a six-amino acid plus hyaluronic acid (6AAH) formulation enriched with tricarboxylic acid (TCA) intermediates to stimulate ECM gene expression. To this aim, human BJ fibroblasts were treated with 6AAH alone or plus succinate or malate alone or succinate plus malate (6AAHSM), and mRNA levels of several ECM markers were evaluated. 6AAHSM increased the expression of all the ECM markers significantly above 6AAH alone or plus only succinate or malate. Furthermore, in an in vitro oxidative damage model, 6AAHSM blunted the hydrogen peroxide-induced decline in ECM gene expression. Our data suggest that feeding cells with 6AAH enriched with TCAs could efficiently be employed as a non-pharmacological approach for counteracting skin aging.

Conjugate compounds constitute a new class of molecules of important biological interest mainly for the treatment of diseases such as cancer. The N-terminus region of cationic peptides has been described as important for their biological activity. The aim of this study was to evaluate the lytic peptide Hecate (FALALKALKKALKKLKKALKKAL) and the effect of conjugating this macromolecule with gallic acid (C7H6O5) in terms of structure, anti-cancer activity, and toxicity. An N-terminus GA-Hecate peptide conjugate was synthesized to provide information regarding the relationship between the amino-terminal region and its charge and the secondary structure and biological activity of the peptide; and the effects of gallic acid on these parameters. Peptide secondary structure was confirmed using circular dichroism (CD). The CD measurements showed that the peptide has a high incidence of α-helical structures in the presence of SDS and LPC, while GA-Hecate presented lower incidence of α-helical structures in the same chemical environment. An evaluation of the anti-cancer activity in HeLa cancer cells indicated that both peptides are active, but that coupling gallic acid at the N-terminus decreased the activity of the free peptide. GA-Hecate showed lower activity in non-tumor keratinocyte cells but higher hemolytic activity. Our findings suggest that the N-terminus of Hecate plays an important role in its activity against cervical cancer by affecting it secondary structure, toxicity, and hemolytic activity. This study highlights the importance of the N-terminus in antitumor activity and could provide an important tool for developing new anti-cancer drugs.

A peptide heterodimer comprises two different receptor-targeting peptide ligands. Molecular imaging probes based on dual-receptor targeting peptide heterodimers exhibit improved tumor targeting efficacy for multi-receptor expressing tumors compared with their parent single-receptor targeting peptide monomers. Previously we have developed bombesin (BBN)-RGD (Arg-Gly-Asp) peptide heterodimers, in which BBN and RGD are covalently connected with an asymmetric glutamate linker (J Med Chem 52:425–432, 2009). Although 18F-labeled heterodimers showed significantly better microPET imaging quality than 18F-labeled RGD and BBN monomers in a PC-3 xenograft model which co-expresses gastrin-releasing peptide receptor (GRPR) and integrin αvβ3, tedious heterodimer synthesis due to the asymmetric nature of glutamate linker restricts their clinical applications. In this study, we report the use of a symmetric linker AEADP [AEADP = 3,3′-(2-aminoethylazanediyl)dipropanoic acid] for the synthesis of BBN-RGD peptide heterodimer. The 18F-labeled heterodimer (18F-FB-AEADP-BBN-RGD) showed comparable microPET imaging results with glutamate linked BBN-RGD heterodimers, indicating that the replacement of glutamate linker with AEADP linker did not affect the biological activities of BBN-RGD heterodimer. The heterodimer synthesis is rather easy and straightforward. Because tumors often co-express multiple receptors, the use of a symmetric linker provides a general method of fast assembly of various peptide heterodimers for imaging multi-receptor expressing tumors.

We report on a simple synthetic route to a novel anthracene-based bis-armed amino acid derivative as a useful fluorescent probe. Various photophysical studies of this amino acid derivative are also described. Here, Suzuki–Miyaura cross-coupling reaction has been used as a key step for carbon–carbon bond formation.

The synthesis of unnatural amino acids plays a key part in expanding the potential application of peptide-based drugs and in the total synthesis of peptide natural products. Herein, we report a direct method for the synthesis of orthogonally protected 5-membered heteroaromatic amino acids.

The aim of the present study was to evaluate the preventive effects of taurine (TAU) supplementation upon monosodium glutamate (MSG)-induced obesity. Rats treated during the first 5 days of life with MSG or saline were distributed into the following groups: control (CTL), CTL-treated with TAU (CTAU), MSG and MSG-supplemented with TAU (MTAU). CTAU and MTAU received 2.5% of TAU in their drinking water from 21 to 90 days of life. At the end of treatment, MSG and MTAU rats were hyperinsulinemic, glucose intolerant and insulin resistant, as judged by the HOMA index. MSG and MTAU rat islets secreted more insulin at 16.7 mM glucose compared to CTL. MSG rats also showed higher triglycerides (TG) and non-esterified fatty acids (NEFA) plasma levels, Lee Index, retroperitoneal and periepidydimal fat pads, compared with CTL, whereas plasma lipid concentrations and fat depots were lower in MTAU, compared with MSG rats. In addition, MSG rats had a higher liver TG content compared with CTL. TAU decreased liver TG content in both supplemented groups, but fat content only in MTAU rats. TAU supplementation did not change glucose homeostasis, insulin secretion and action, but reduced plasma and liver lipid levels in MSG rats.