N-Phosphoryl amino acids (NPAAs) are a novel series of N-terminal-activated amino acids that act as the energy source and phosphoryl donor in intra- and intermolecular phosphoryl transfer to form “high-energy” species, such as acetyl phosphate and aminoacyl phosphates, and in the self-assembled synthesis of polypeptides under mild aqueous conditions. In this work, the chemical reactivity of N-mono(methoxyphosphoryl)glycine as a representative was investigated in detail by using a combination of the stable-isotope-labeling (¹⁵N) technique, ³¹P NMR, ESI-MS/MS and LC-MS. The phosphoryl group of NPAAs can be transferred intermolecularly to the carboxy group of another molecule through intramolecular cyclic pentacoordinate phosphoric–amino acid anhydride intermediates. In addition to C-terminal activation by phosphate anhydride, amino acids can also be self-activated by N-phosphorylation. This information not only provides some interesting clues for understanding the active role of the phosphoryl group in living systems, but also shows that the origin of life might be attributed to the chemical evolution of N-phosphoryl amino acids.

A new family of artificial transcription factor (ATF)-based conjugates have been designed and synthesized as potent chemical nucleases. Polyamides as the important and efficient ATFs were used to modify and activate several anchor compounds. The results demonstrate that the resulting conjugates remarkably promote the rate accelerations and non-random double-strand DNA cleavage activity. Interestingly, the cleavage activity of both the hydrolytic and oxidative agents was promoted efficiently through the modification of the ATFs.

Vibrational circular dichroism (VCD) spectroscopic measurements and density functional theory (DFT) calculations have been used to obtain the absolute structural information about four sets of diastereomers of pentacoordinate spirophosphoranes derived separately from l- (or d-) valine and l- (or d-) leucine for the first time. Each compound contains three stereogenic centers: one at the phosphorus center and two at the amino acid ligands. Extensive conformational searches for the compounds have been carried out and their vibrational absorption (VA) and VCD spectra have been simulated at the B3LYP/6-311++G** level. Although both VA and VCD spectra are highly sensitive to the structural variation of the apical axis, that is, the OPO or NPO arrangement, the rotamers generated by the aliphatic amino side chains show little effect on both. The dominant experimental VCD features in the 1100–1500 cm⁻¹ region were found to be controlled by the chirality at the phosphorus center, whereas those at the CO stretching region are determined by the chirality of the amino acid ligands. The good agreement between the experimental VA and VCD spectra in CDCl₃ solution and the simulated ones allows us to assign the absolute configurations of these pentacoordinate phosphorus compounds with high confidence. This study shows that the VCD spectroscopy complemented with DFT calculations is a powerful and reliable method for determining the absolute configurations and dominating conformers of synthetic phosphorus coordination complexes in solution.

Cyclic acylphosphoramidates (2-hydroxy-2-oxy-1,3,2-oxazaphospholidine-5-ones, CAPAs) are phosphate-activated amino acids possessing both a carboxyl–phosphoryl anhydride and a phosphoramidate bond in a ring. They structurally resemble NCAs (amino acid N-carboxyanhydrides,Leuchs' anhydrides), which have been extensively investigated. By contrast, the chemistry of CAPAs has remained almost unexplored since it was proposed in a prebiotic reaction of inorganic polyphosphates (PolyPs) with amino acids. In the present work, the bielectrophilicity of α-CAPAs (Gly-CAPA, Ala-CAPA) was identified by isotopic analysis (¹⁸O, ¹⁵N) and further proved by trapping α-CAPA with nucleophiles such as water, amino acids, phosphate and methanol in alkaline media, which yielded N-phosphoamino acids and peptide phosphoanhydride and phosphate ester derivatives. By comparison with the reactivity of NCAs, the bielectrophilicity of CAPAs indicates that CAPAs can provide rich chemistry.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)