Structure of Antibody-Bound Peptides and Retro−Inverso Analogues. A Transferred Nuclear Overhauser Effect Spectroscopy and Molecular Dynamics Approach^,

Abstract

The three-dimensional structures of the two L-peptides, H-CGGIRGERA-OH, called L(A), and H-CGGIRGERG-OH, called L(G), corresponding or close to the IRGERA sequence present in the C-terminal region (residues 130-135) of histone H3, and their retro-inverso analogues HO-mAreGriGGC-NH2, called RI(mA), and HO-mGreGriGGC-NH2, called RI(mG), have been studied by two-dimensional 1H NMR and molecular dynamics calculations in association with a monoclonal antibody generated against L(A). At 25 degrees C, the affinity constants of the monoclonal antibody with respect to RI(mA) and RI(mG) were 75- and 270-fold higher than those measured with the homologous L(A) and L(G) peptides, respectively. Due to the spontaneous epimerization of the mA malonic residue, RI(mA) gave rise to two sets of resonances. With regard to the NH amide region, one set was similar to that for RI(mG) while the second was similar to those for the parent L-peptides L(A) and L(G). The antibody-bound conformations of the two couples of L- and retro-inverso peptides have been analyzed using molecular modeling calculations based on the transferred NOE interproton distances. Folded structures appeared in both cases with a type II' beta-turn in the parent GGIR sequence and a type I' beta-turn in the retro-inverso reGr sequence.

The Nuclear Overhauser Effect in the Lead Identification Process Pharmacophore Models

“…Since then, the tr-NOE technique has been used to analyze the conformational properties of several peptides bound to proteins and antibodies [55][56][57][58][59][60][61][62]. Works related to complexes between sugar and proteins [63,64] or sugar and antibodies [65] have also been performed.…”

Peptide–protein interactions studied by surface plasmon and nuclear magnetic resonances

“…A strong correlation between the structure stability and the a¤nity between protein subdomains has been found from SPR data [2] and a combined use of SPR and NMR measurements has been proposed for investigating peptide^antibody [3,4] and virus^receptor interactions [5].…”

The partial retro–inverso modification: A road traveled together

“…Two-dimensional (2D) 1 H-NMR studies and molecular dynamic calculations of histone H3[127-135], C-G-G-I-R-G-E-R-A, its Gly 135 analog, and the corresponding C-terminal malonyl-containing endgroup modified RI isomers in the presence of the mAb-generated against histone H3[127-135] were carried out by Phan-Chan-Du and coworkers. 42 The mA-and mG-containing end-group modified RI peptides cross reacted with the mAb with affinities that were 75-and 270-fold higher than those with the respective homologous all-L peptides. D-R 2 , and A 9 /(R)-mA 1 have the same orientation with respect to the backbone in both the all-L and RI peptides.…”