13716-72-8Relevant articles and documents
The complexation of peptides by aminocyclodextrins
Hacket, Frank,Simova, Svetlana,Schneider, Hans-Joerg
, p. 159 - 170 (2001)
Four β-cyclodextrins (CDs) were prepared bearing either an (N,N-dimethylamino)propylamino group (1), an (N-methyl)-piperazino group (2) or a benzylamino group (3), or seven methylamino susbtituents (4). Association constants K in water with di- and tripeptides reach up to 200 M-1, and after protection at the N-terminus up to 680 M-1. Appreciable binding occurs only in the presence of lipophilic amino acid side-chains, with preference for this at the C-terminus. A moderate sequence and side-chain selectivity is observed with 1, 2 and 3, but less so with the highly charged 4 where ion pairing dominates. Detailed NMR analyses with advanced techniques including T-ROESY and GHSQC allow full assigment of most 1H and 13C signals, with extraction of many substituent and complexation induced shifts changes (SIS and CIS values, respectively). The CIS values and NOE cross peaks from ROESY experiments provide for insight into the binding modes of selected complexes, indicating, e.g., the simultaneous presence of complexes with a peptide phenyl unit approaching from both the narrow and the wide side of the CD cavity. With 3 one observes self-inclusion of the pendant phenyl ring within the cavity, and its replacement by analytes such as peptides, or by adamantanecarboxylic acid. The inclusion modes are illustrated with force field simulated structures and many NMR spectra, which are made available in electronic supplements. Copyright
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.
Asymmetric Synthesis of Peptides
Kleemann, Axel,Martens, Juergen,Samson, Marc,Bergstein, Wolfgang
, p. 740 - 741 (2007/10/02)
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