119595-77-6Relevant academic research and scientific papers
Potentially macrocyclic peptidyl boronic acids as chymotrypsin inhibitors
Tian, Zong-Qiang,Brown, Bradley B.,Mack, David P.,Hutton, Craig A.,Bartlett, Paul A.
, p. 514 - 522 (2007/10/03)
The possibility of forming a peptide boronate adduct in a serine protease active site that mimics the first tetrahedral intermediate in the peptide hydrolysis mechanism was explored with the complex boronic acid analogs 7, 8-OH, and 8-NH2. In these structures, the P1 and P2 residues and the P1'-P3' residues are connected through the P2 and P1' side chains, to encourage formation of the diester or amide-ester adducts via macrocyclization. These inhibitors were assembled from suitably protected derivatives of 2,4-diaminobutanoic acid or 2,4-diaminopentanoic acid (11), borophenylalanine (12), aspartic acid, malic acid or the substituted malic acid analog 13, and Leu-Arg dipeptide. Stereoselective syntheses were developed for the (S,S)-2,4-diaminopentanoate 11 and for the (S,S)-β-isobutylmalate 13 derivatives. The complex peptidyl boronates 7 (K(i) = 26 nM) and 8-OH (68 nM) are potent inhibitors of α-chymotrypsin; however, the affinity of 7 is neither time- nor pH-dependent, and it is only moderately greater than that found for comparison compounds like 8-H (114 nM), 9 (356 nM), and 16 (219 nM) that cannot cyclize or form a diester adduct.
Synthesis of 4-Substituted Prolines as Conformationally Constrained Amino Acid Analogues
Koskinen, Ari M. P.,Rapoport, Henry
, p. 1859 - 1866 (2007/10/02)
Anionic substitution of N-(9-(9-phenylfluorenyl))-protected glutamic acid esters proceeds without loss of optical integrity to give 4-substituted glutamic acid derivatives.The 4-methyl, propyl, cyanomethyl, and phenyl analogues have thus been prepared.Pri
