84794-59-2Relevant academic research and scientific papers
Peptide ligation by chemoselective aminonitrile coupling in water
Canavelli, Pierre,Islam, Saidul,Powner, Matthew W.
, p. 546 - 549 (2019/07/18)
Amide bond formation is one of the most important reactions in both chemistry and biology1–4, but there is currently no chemical method of achieving α-peptide ligation in water that tolerates all of the 20 proteinogenic amino acids at the peptide ligation site. The universal genetic code establishes that the biological role of peptides predates life’s last universal common ancestor and that peptides played an essential part in the origins of life5–9. The essential role of sulfur in the citric acid cycle, non-ribosomal peptide synthesis and polyketide biosynthesis point towards thioester-dependent peptide ligations preceding RNA-dependent protein synthesis during the evolution of life5,9–13. However, a robust mechanism for aminoacyl thioester formation has not been demonstrated13. Here we report a chemoselective, high-yielding α-aminonitrile ligation that exploits only prebiotically plausible molecules—hydrogen sulfide, thioacetate12,14 and ferricyanide12,14–17 or cyanoacetylene8,14—to yield α-peptides in water. The ligation is extremely selective for α-aminonitrile coupling and tolerates all of the 20 proteinogenic amino acid residues. Two essential features enable peptide ligation in water: the reactivity and pKaH of α-aminonitriles makes them compatible with ligation at neutral pH and N-acylation stabilizes the peptide product and activates the peptide precursor to (biomimetic) N-to-C peptide ligation. Our model unites prebiotic aminonitrile synthesis and biological α-peptides, suggesting that short N-acyl peptide nitriles were plausible substrates during early evolution.
Peptide ligation by chemoselective aminonitrile coupling in water
Canavelli, Pierre,Islam, Saidul,Powner, Matthew W.
, p. 546 - 549 (2019/07/31)
Amide bond formation is one of the most important reactions in both chemistry and biology1–4, but there is currently no chemical method of achieving α-peptide ligation in water that tolerates all of the 20 proteinogenic amino acids at the pepti
N-acyl dipeptides and their compositions
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, (2008/06/13)
Novel a-acyl dipeptides of the formula: in which AS, R1 and R2 have certain, more precisely defined meanings. These N-acyl dipeptides are more stable under conditions of sterilization (121° C.) than corresponding, non-acylated dipept
Serine-Protease-Assisted Synthesis of Peptide Substrates for α-Chymotripsin
Bizzozero, Spartaco A.,Rovagnati, Bruno A.,Dutler, Hans
, p. 1707 - 1719 (2007/10/02)
δ-Chymotrypsin catalyzes peptide-bond formation between acylated amino-acid and peptide esters as the carboxyl component and amino-acid and peptide amides as the amino component.The conditions under which enzyme-catalyzed coupling can be used for fragment condensation in peptide synthesis is investigated.To illustrate the method the synthesis of tetra-, penta and hexapeptides of the structure Ac-Lxn-...-Lxl-Lyl-...-Lym-NH2 with Lxl = Tyr, designed as substrates for α-chymotrypsin is described.
