Intermolecular Phosphoryl Transfer of N‐Phosphoryl Amino Acids

Abstract

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 ((15)N) technique, (31)P 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.National Natural Science Foundation of China (NSFC)[21075103, 20972130, 20805037, 20732004

Rapid Mechanochemical Synthesis of Amides with Uronium-Based Coupling Reagents, a Method for Hexa-amidation of Biotin[6]uril

“…In the 13 C NMR spectrum, carbonyl group 17 showed a doublet signal at δ = 168.1 ppm (JCP = 8.8 Hz), due to its coupling with the neighboring phosphorus. 65 Significantly lower yields of 17 were attained with K3PO4 or with TCFH as coupling reagent (Figure 2). The reaction of acetic acid with K4P2O7 produced acetyl pyrophosphate 18 in a 50% yield, according to 31 P-NMR analysis.…”

“…We speculated that phosphate salts could additionally contribute to the activation of the carboxyl substrate 2 via the formation of acyl phosphate intermediates containing a "high-energy" phosphoester bond, prone to easy nucleophilic amine attack. 65,66 Interestingly, the same pathway is also involved in the ATP-dependent biosynthesis of amide bond-containing biomolecules. 11 The plausibility of our assumption is further supported by existing literature showing that acyl phosphates can be indeed generated in solution by the DCC-mediated coupling of carboxylic acids with phosphate salts.…”

Current trends in isotope‐coded derivatization liquid chromatographic‐mass spectrometric analyses with special emphasis on their biomedical application

“…Zhang et al () reported another example for NHS esters capable of undergoing diastereomeric ICD: stable isotope N ‐phosphoryl amino‐acid labeling (SIPAL) strategy. SIPAL is based on using duplex ICD reagents, 18 O 0 ‐ and 18 O 2 ‐ N ‐diisopropyl phosphoryl L‐alanine N ‐hydroxysuccinimide esters ( 18 O 0 / 18 O 2 ‐DIPP‐L‐Ala‐NHS), which were designed and synthesized based on organic phosphorus chemistry (Gao et al, ; Ji et al, ). First, 18 O 0 / 18 O 2 ‐diphenyl phosphite was reacted with isopropanol producing 18 O 0 / 18 O 2− diisopropyl H‐phosphite ( 18 O 0 / 18 O 2 ‐DIPP‐H) by intramolecular phosphoryl transfer (Gao et al, ).…”

“…SIPAL is based on using duplex ICD reagents, 18 O 0 ‐ and 18 O 2 ‐ N ‐diisopropyl phosphoryl L‐alanine N ‐hydroxysuccinimide esters ( 18 O 0 / 18 O 2 ‐DIPP‐L‐Ala‐NHS), which were designed and synthesized based on organic phosphorus chemistry (Gao et al, ; Ji et al, ). First, 18 O 0 / 18 O 2 ‐diphenyl phosphite was reacted with isopropanol producing 18 O 0 / 18 O 2− diisopropyl H‐phosphite ( 18 O 0 / 18 O 2 ‐DIPP‐H) by intramolecular phosphoryl transfer (Gao et al, ). Second, 18 O 0 / 18 O 2 ‐DIPP‐H were reacted with alanine forming 18 O 0 / 18 O 2 ‐DIPP‐L‐Ala.…”

Effects of Trimetaphosphate on Abiotic Formation and Hydrolysis of Peptides

“…Trimetaphosphate (P 3 ) could have been made directly from an acidic phosphate as a byproduct of volcanic processing [ 3 , 13 ]. More recently, the structural characterization of N -phosphoryl amino acids and the formation of the P–N bond have been elucidated by NMR [ 14 ] and IR [ 15 ] analysis, which have provided significant insight into the reaction mechanism [ 16 ]. Despite quite extensive studies on the activation of amino acids by polyphosphates, little effort has been devoted to study the subsequent dehydration (or condensation) reactions resulting in polypeptide formation.…”