1009319-48-5Relevant articles and documents
Evaluation of the antibacterial and antibiofilm activities of novel CRAMP-vancomycin conjugates with diverse linkers
Mishra, Nigam M.,Briers, Yves,Lamberigts, Chris,Steenackers, Hans,Robijns, Stijn,Landuyt, Bart,Vanderleyden, Jos,Schoofs, Liliane,Lavigne, Rob,Luyten, Walter,Van Der Eycken, Erik V.
, p. 7477 - 7486 (2015)
We report the design, synthesis and antibacterial activity analysis of conjugates of vancomycin and cathelicidin-related antimicrobial peptides (CRAMP). Vancomycin inhibits the nascent peptidoglycan synthesis and is highly active against Gram-positive bacteria, whereas Gram-negative bacteria are generally insensitive due to a protective outer membrane. CRAMP is known to translocate across the Gram-negative outer membrane by a self-promoted uptake mechanism. Vancomycin-CRAMP conjugates were synthesized using click chemistry with diverse hydrophilic and hydrophobic linkers, with CRAMP functioning as a carrier peptide for the transfer of vancomycin through the outer membrane. Small hydrophobic linkers with an aromatic group result in the most active conjugates against planktonic Gram-negative bacteria, while maintaining the high activity of vancomycin against Gram-positive bacteria. These conjugates thus show a broad-spectrum activity, which is absent in CRAMP or vancomycin alone, and which is strongly improved compared to an equimolar mixture of CRAMP and vancomycin. In addition, these conjugates also show a strong inhibitory activity against S. Typhimurium biofilm formation.
Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents
Kayser-Bricker, Katherine J.,Glenn, Matthew P.,Lee, Sang Hoon,Sebti, Said M.,Cheng, Jin Q.,Hamilton, Andrew D.
supporting information; experimental part, p. 1764 - 1771 (2009/09/05)
Akt has emerged as a critical target for the development of anti-cancer therapies. It has been found to be amplified, overexpressed, or constitutively activated in numerous human malignancies with oncogenesis derived from the simultaneous promotion of cell survival and suppression of apoptosis. A valuable alternative to the more common ATP-mimetic based chemotherapies is a substrate-mimetic approach, which has the potential advantage of inherent specificity of the substrate-binding pocket. In this paper we present the development of high affinity non-peptidic, substrate-mimetic inhibitors based on the minimum GSK3β substrate sequence. Optimization of initial peptidic leads resulted in the development of several classes of small molecule inhibitors, which have comparable potency to the initial peptidomimetics, while eliminating the remaining amino acid residues. We have identified the first non-peptidic substrate-mimetic lead inhibitors of Akt 29a-b, which have affinities of 17 and 12 μM, respectively. This strategy has potential to provide a useful set of molecular probes to assist in the validation of Akt as a potential target for anti-cancer drug design.
A submicrogram-scale protocol for biomolecule-based PET imaging by rapid 6π-azaelectrocyclization: Visualization of sialic acid dependent circulatory residence of glycoproteins
Tanaka, Katsunori,Masuyama, Tatsuro,Hasegawa, Koki,Tahara, Tsuyoshi,Mizuma, Hiroshi,Wada, Yasuhiro,Watanabe, Yasuyoshi,Fukase, Koichi
, p. 102 - 105 (2008/09/19)
On target: Lysine residues in picomole samples of a peptide, proteins, and a monoclonal antibody were rapidly and selectively labeled by a dota-based probe (1, see scheme). Positron emission tomography imaging of [68Ca]dota- labeled orosomucoid
