849100-67-0Relevant academic research and scientific papers
Bioinspired Amphiphilic Peptide Dendrimers as Specific and Effective Compounds against Drug Resistant Clinical Isolates of E. coli
Sowińska, Marta,Laskowska, Anna,Gu?piel, Adam,Solecka, Jolanta,Bochynska-Czyz, Marta,Lipkowski, Andrzej W.,Trzeciak, Katarzyna,Urbanczyk-Lipkowska, Zofia
, p. 3571 - 3585 (2018/10/24)
Evolution-derived natural compounds have been inspirational for design of numerous pharmaceuticals, e.g., penicillins and tetracyclines. Herein, we present a bioinspired strategy to design peptide dendrimers for the effective therapy of E. coli infections where the selection of appropriate amino acids and the mode of their assembly are based on the information gained from research on membranolytic natural antimicrobial peptides (AMP's). On the molecular level two opposite effects were explored: the effect of multiple positive charges necessary for membrane disintegration was equilibrated by the anchoring role of tryptophanes. Indeed, a series of Trp-terminated dendrimers exhibited high potency against clinical isolates of antibiotic resistant ESBL E. coli strains, stability in human plasma along with very low hemo- and genotoxicity. Investigation of the underlying antimicrobial mechanism indicated that the dendrimers studied at minimal inhibitory concentration showed weak permeability toward membranes. Solid-state 2D NMR studies revealed their presence on and inside the model membranes. Therefore, their biological properties might be explained by targeting of extra- or intracellular receptors. Our results point to a new approach to design novel branched antimicrobials with high therapeutic index.
Synthesis of novel dendrimeric systems containing NLO ligands
Brouwer, Arwin J.,Liskamp, Rob M. J.
, p. 487 - 495 (2007/10/03)
The convergent synthesis of novel dendrimeric systems containing NLO-ligands is described. The poor solubility properties of dendrimers of type A containing NLO-ligands enticed us into developing novel dendrimers of type B leading to the convergent synthesis of third generation NLO-containing dendrimer 15 containing branches of unequal length. Furthermore, a strategy was developed for connection of dendrons leading to dendrimer-to-dendrimer systems of type C. For this a dendrimer was required of which selectively one branch could be deprotected i.e. dendrimer 22. To the deprotected branch a next dendrimer moiety was attached leading to 23, also containing a deprotectable branch, which was used for attachment of another dendrimer moiety, leading to dendrimer-to- dendrimer system 24. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
