33900-05-9Relevant academic research and scientific papers
Relaxivity and transmetallation stability of new benzyl-substituted derivatives of gadolinium-DTPA complexes
Laurent, Sophie,Botteman, Francois,Vander Elst, Luce,Muller, Robert N.
, p. 1077 - 1089 (2007/10/03)
In our efforts of finding new specific contrast agents of higher relaxivity and selectivity, we have prepared the two new benzyl-functionalized DTPA ('diethylenetriamine pentaacetate') gadolinium complexes (S)-3 and (R,S)-4, and compared their properties with those of the known regioisomers (S)-2 and (S)-1. The theoretical fitting of the reduced transverse relaxation rates of the 17O-nucleus of H2O gave values for the water-residence time (τM) of 86-143 ns at 310 K, values that are not limiting the proton relaxivity at body temperature. 1H-NMRD (nuclear magnetic-relaxation dispersion) Profiles showed that the relaxivity of 1-4 (r1=4.3-5.1 s-1 mM-1 at 20 MHz and 310 K) is higher than for the Gd-DTPA parent compound 5. Transmetallation assessment demonstrated that all substituted compounds, except for (S)-2, are more stable than 5. The highest stability towards Zn2+-induced transmetallation was achieved with complexes 3, 1, and 4 (in decreasing order). Apparently, the steric hindrance of the benzyl substituents in positions 5, 4, and 2, respectively, favorably reduces the accessibility of Zn ions. From a synthetic point of view, 4-substituted DTPA complexes of type 1 are more readily accessible than 5-substituted compounds of type 3. Therefore, the former seem to be superior for linking substituted DTPA complexes to macromolecules or specific vectors.
Partially modified retro-inverso pseudopeptides as non-natural ligands for the human class I histocompatibility molecule HLA-A2
Guichard, Gilles,Connan, Francine,Graff, Roland,Ostankovitch, Marina,Muller, Sylviane,Guillet, Jean-Gérard,Chopping, Jeannine,Briand, Jean-Paul
, p. 2030 - 2039 (2007/10/03)
Syntheses of a series of partially modified retro-inverso analogues of the antigenic peptide M58-66 derived from the influenza virus matrix protein are reported. The retro-inverso modification Ψ(NH-CO) was obtained by replacement of two successive amino acid residues with a 2-substituted malonate derivative and gem-diaminoalkyl residue. The resulting compounds 1- 8 were tested for their binding to the human histocompatibility class I molecule HLA-A2 in an assembly assay using lysates of peptide transporter- deficient cells T2. Specific peptide-dependent HLA-A2 assembly was revealed by an enzyme-linked immunosorbent assay. Significant HLA-A2 assembly was detected in the presence of analogues [gGly58-(S)mLeu59]-M58-66 (1a), [gGly61-(R,S)mPhe62]M58-66 (4), [gVal63-(R,S)mPhe64]M58-66 (6), and [gPhe64(R,S)mAla65]M58-66 (7). The introduction of the retro-inverso modification between P2-P3, P3-P4, P5-P6, and P8-P9 (compounds 2, 3, 5, and 8, respectively) however led to a dramatic reduction in peptide binding to HLA-A2. Interestingly, compound 1a which contains modification between P1-P2 was found to be the most potent analogue, being able to retain the original HLA-A2 binding profile of the parent peptide M58-66. Taken together, these results and recent binding data obtained in the context of murine MHC class I molecule H-2K(d) suggest that the incorporation of peptide bond surrogates in MHC class I-restricted epitopes is a useful approach to design molecules having both increased stability and high MHC-binding capacity. Depending on their agonist or antagonist effects at the T-cell receptor, such non-natural MHC ligands are likely to find many applications in the development of peptide-based vaccines or as potential therapeutic agents in the treatment of allergies and autoimmune diseases.
Carboxyl-Modified Amino Acids and Peptides as Protease Inhibitors
Thompson, Stewart A.,Andrews, Peter R.,Hanzlik, Robert P.
, p. 104 - 111 (2007/10/02)
Several types of carbonyl-modified amino acids and peptides were prepared in forms having N-terminal modifications (carrier fragments) suitable for one of several representative protease enzymes, and their inhibitory action toward those enzymes were evalu
A NEW SYNTHESIS OF PARTIALLY MODIFIED retro-inverso ENKEPHALINAMIDES
Squadrini, Fabio,Verdini, Antonio Silvio,Viscomi, Giuseppe Claudio
, p. 25 - 30 (2007/10/02)
A new synthesis of a potent, long-acting enkephalinamide analogue is described in which the incorporation of a gem-diaminoalkyl residue into the peptide backbone is accomplished via a Hofmann rearrangement of a fully protected peptidyl amide to amine carr
