Heteroclitic properties of mixed alpha- and aza-beta3-peptides mimicking a supradominant CD4 T cell epitope presented by nucleosome.

Recent studies have revealed that peptide analogues containing modified peptide bonds might replace poorly stable natural peptides in therapeutic strategies. Using the model peptide 88-99 of histone H4, which contains a supradominant epitope recognized by Th cells induced to nucleosomes, we have generated twelve analogues containing aza-beta(3)-amino acid residue substitutions. The ability of this new class of peptidomimetics corresponding to the Psi[CONHNRCH(2)] modification to be recognized by T cells primed with the parent peptide was examined in BALB/c mice.

Solid-phase synthesis of "mixed" peptidomimetics using Fmoc-protected aza-beta3-amino acids and alpha-amino acids.

[structure: see text] A solid-phase fluorenylmethyloxycarbonyl (Fmoc)-based synthesis strategy is described for "mixed" aza-beta3-peptides as well as a convenient general approach for their required building blocks, the aza-beta3-amino acid residues (aza-beta3-aa). These monomers allow the synthesis of relatively large quantities of pure mixed aza-beta3-peptides. The required Fmoc-substituted aza-beta3-amino acids are accessible by convenient synthesis, and a number of monomers including those containing side chains with functional groups have been synthesized.

Synthesis and evaluation of new omega-borono-alpha-amino acids as rat liver arginase inhibitors.

Recent studies have demonstrated that arginase plays important roles in pathologies such as asthma or erectile dysfunctions. We have synthesized new omega-borono-alpha-amino acids that are analogues of the previously known arginase inhibitors S-(2-boronoethyl)-l-cysteine (BEC) and 2-amino-6-boronohexanoic acid (ABH) and evaluated them as inhibitors of purified rat liver arginase (RLA). In addition to the distance between the B(OH)(2) and the alpha-amino acid functions, the position of the sulfur atom in the side chain also appears as a key determinant for the interaction with the active site of RLA.