808733-47-3Relevant articles and documents
Aza-β3-amino acid containing peptidomimetics as cAMP-dependent protein kinase substrates
Kisseljova, Ksenija,Kuznetsov, Aleksei,Baudy-Floc'H, Michle,Jaerv, Jaak
supporting information; experimental part, p. 229 - 233 (2010/10/01)
Peptidomimetic analogs of the peptide RRASVA, known as the "minimal substrate" of the catalytic subunit of the cAMP-dependent protein kinase (PKA), were synthesized by consecutive replacement of natural amino acids by their aza-β3 analogs. The peptidomimetics were tested as PKA substrates and the kinetic parameters of the phosphorylation reaction were determined. It was found that the interaction of these peptidomimetics with the enzyme active center was sensitive to the location of the backbone modification, while the maximal rate of the reaction was practically not affected by the structure of substrates. The pattern of molecular recognition of peptidomimetics was in agreement with the results of structure modeling and also with the results of computational docking study of peptide and peptidomimetic substrates with the active center of PKA. It was concluded that the specificity determining factors which govern substrate recognition by the enzyme should be grouped along the phosphorylatable substrate, and such clustering might open new perspectives for pharmacophore design of peptides and peptide-like ligands.
Solid-phase synthesis of "mixed" peptidomimetics using Fmoc-protected aza-β3-amino acids and α-amino acids
Busnel, Olivier,Bi, Lanrong,Dali, Hayet,Cheguillaume, Arnaud,Chevance, Soizic,Bondon, Arnaud,Muller, Sylviane,Baudy-Floc'h, Michele
, p. 10701 - 10708 (2007/10/03)
A solid-phase fluorenylmethyloxycarbonyl (Fmoc)-based synthesis strategy is described for "mixed" aza-β3-peptides as well as a convenient general approach for their required building blocks, the aza-β3-amino acid residues (aza-β3-aa). These monomers allow the synthesis of relatively large quantities of pure mixed aza-β3-peptides. The required Fmoc-substituted aza-β3-amino acids are accessible by convenient synthesis, and a number of monomers including those containing side chains with functional groups have been synthesized. The method was applied toward the solid-phase ynthesis of aza-β3-peptide mimetics of a biologically active histone H4 sequence.
