204251-86-5Relevant articles and documents
High affinity surface binding of a strongly dimerizing vancomycin-group antibiotic to a model of resistant bacteria
O'Brien, Dominic P.,Entress, Richard M. H.,Cooper, Matthew A.,O'Brien, Simon W.,Hopkinson, Andrew,Williams, Dudley H.
, p. 5259 - 5265 (1999)
The factors that give rise to binding enhancements when a strongly dimerizing vancomycin-group antibiotic (chloroeremomycin) binds to a model cell surface of vancomycin-resistant enterococci (VRE) have been semiquantitated. The model cell surface is comprised of vesicles to which have been anchored cell wall precursor analogues of vancomycin-resistant bacteria (which terminate in -D-lactate) via a hydrophobic docosanoyl (C22) chain. Using 1H and 19F NMR spectroscopy, a large binding enhancement at the model cell surface (compared to the binding of an analogous ligand in free solution) has been observed. This enhancement can be partitioned into two distinct factors: a simple concentrating factor arising from an increase in local concentration of ligand when it is located at the vesicle surface and a factor arising from the cooperative interaction of species mutually bound to the membrane surface. The overall enhancement to binding at a surface compared to binding in free solution was found to be a factor of 102-103. In contrast, no significant surface binding enhancement was observed for the weakly dimerizing antibiotic vancomycin.
Structure-activity relationships in nucleotide oligomerization domain 1 (Nod1) agonistic γ-glutamyldiaminopimelic acid derivatives
Agnihotri, Geetanjali,Ukani, Rehman,Malladi, Subbalakshmi S.,Warshakoon, Hemamali J.,Balakrishna, Rajalakshmi,Wang, Xinkun,David, Sunil A.
, p. 1490 - 1510 (2011/04/24)
N-Acyl-γ-glutamyldiaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C12-γ-d-Glu-DAP. Analogues with glutaric or γ-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity. Substitution of the meso-diaminopimelic (DAP) acid component with monoaminopimelic acid, l- or d-lysine, or cadaverine also results in reduced activity. The free amine on DAP is crucial. However, the N-acyl group on the d-glutamyl residue can be substituted with N-alkyl groups with full preservation of activity. The free carboxylates on the DAP and Glu components can also be esterified, resulting in more lipophilic but active analogues. Transcriptomal profiling showed a dominant up-regulation of IL-19, IL-20, IL-22, and IL-24, which may explain the pronounced Th2-polarizing activity of these compounds and also implicate cell signaling mediated by TREM-1. These results may explain the hitherto unknown mechanism of synergy between Nod1 and TLR agonists and are likely to be useful in designing vaccine adjuvants.
On-bead synthesis and binding assay of chemoselectively template-assembled multivalent neoglycopeptides
Renaudet, Olivier,Dumy, Pascal
, p. 2628 - 2636 (2008/09/21)
The investigation of recognition events between carbohydrates and proteins, especially the control of how spatial factors and binding avidity are correlated in, remains a great interest for glycomics. Therefore, the development of efficient methods for the rapid evaluation of new ligands such as multivalent glycoconjugates is essential for diverse diagnostic or therapeutic applications. In this paper we describe the synthesis of chemoselectively- assembled multivalent neoglycopeptides and the subsequent recognition assay on a solid support. Aminooxylated carbohydrates (βLac-ONH2 4, αGalNAc-ONH2 9 and αMan-ONH2 13) have been prepared as carbohydrate-based recognition elements and assembled as clusters onto a cyclopeptidic scaffold by an oxime-based strategy in solid phase. Further binding tests between lectins and beads of resin derivatized with neoglycopeptides displaying clustered lactoses, N-acetylgalactoses and mannoses (18-20) have shown specific recognition and enhanced affinity through multivalent interactions, suggesting that the local density of carbohydrate-based ligands at the bead surface is crucial to improve the interaction of proteins of weak binding affinity. This solid phase strategy involving both molecular assembly and biological screening provides a rapid and efficient tool for various applications in glycomics. The Royal Society of Chemistry 2006.
