The first synthesis and biological activity of a teixobactin analogue is reported. Substitution of the unusual L-allo-enduracididine residue by the naturally occurring L-arginine was achieved, and the analogue gave an activity trend similar to that of teixobactin (against Gram-postive bacteria) and meropenem, which was approved by the FDA in 1996. The synthetic route used allows for the synthesis of the natural product as well as the development of a program of medicinal chemistry.

2-MeTHF and CPME were evaluated as greener alternatives for the most employed solvents in peptide synthesis. The ability of these solvents to dissolve amino acid derivatives and a range of coupling reagents were evaluated as well as the swelling of polystyrene and polyethylene glycol resins. In addition, racemization and coupling efficiencies were also determined. We concluded that the use of 2-MeTHF with combination of DIC/OxymaPure gave the lowest racemization level during stepwise synthesis of Z-Phg-Pro-NH2 and the highest purity during SPPS of Aib-enkephalin pentapeptide (H-Tyr-Aib-Aib-Phe-Leu-NH2).

N,N-Dimethylformamide (DMF), N-methyl-2-pyrrolidone, and dichloromethane (DCM) are the most widely used solvents for Fmoc solid-phase peptide synthesis (SPPS). These solvents are considered hazardous chemicals and are normally used in large amounts for washing, deprotection, and coupling steps. Therefore, the use of these reagents is indeed in question. Our group recently reported the use of 2-methyltetrahydrofuran (2-MeTHF), which is a green solvent, for coupling, but using DMF for the Fmoc removal and washing steps [Amino Acids201648419426.]. Herein, total full green solvent protocols in which DMF and DCM are completely eliminated are reported. Several green solvents, such as 2-MeTHF, ethyl acetate, and isopropyl alcohol; temperature; solid supports; and peptide models were evaluated in this study. The best green protocol established is the use of 2-MeTHF for Fmoc removal, washing, and coupling steps with some more washing with EtOAc at room temperature for a short and challenging peptide (Aib-enkephalin pentapeptide). In the case of a longer and more difficult peptide (Aib-ACP decapeptide), the best protocol established was similar, except for the Fmoc removal and coupling steps that were conducted at 40 °C and in combination with the use of a polyethylene glycol resin (ChemMatrix resin).

Gold nanoparticles (AuNPs) have been extensively used in biological applications because of their biocompatibility, size, and ease of characterization, as well as an extensive knowledge of their surface chemistry. These features make AuNPs readily exploitable for biomedical applications, including drug delivery and novel diagnostic and therapeutic approaches. In a previous work, we studied ex vivo distribution of the conjugate C(AuNP)-LPFFD for its potential uses in the treatment of Alzheimer's disease. In this study, we covalently labeled the conjugate with [(18)F]-fluorobenzoate to study the in vivo distribution of the AuNP by positron emission tomography (PET). After intravenous administration in rat, the highest concentration of the radiolabeled conjugate was found in the bladder and urine with a lower proportion in the intestine, demonstrating progressive accumulation compatible with biliary excretion of the conjugate. The conjugate also accumulated in the liver and spleen. PET imaging allowed us to study the in vivo biodistribution of the AuNPs in a noninvasive and sensitive way using a reduced number of animals. Our results show that AuNPs can be covalently and radioactively labeled for PET biodistribution studies.