84246-49-1Relevant academic research and scientific papers
Orthogonally protected artificial amino acid as tripod ligand for automated peptide synthesis and labeling with [99mTc(OH2) 3(CO)3]+
Shen, Yunjun,Schottelius, Margret,Zelenka, Karel,De Simone, Mariarosaria,Pohle, Karolin,Kessler, Horst,Wester, Hans-Jürgen,Schmutz, Paul,Alberto, Roger
, p. 26 - 35 (2013/03/28)
1,2-Diamino-propionic acid (Dap) is a very strong chelator for the [ 99mTc(CO)3]+ core, yielding small and hydrophilic complexes. We prepared the lysine based Dap derivative l-Lys(Dap) in which the ε-NH2 group was replaced by the tripod through conjugation to its α-carbon. The synthetic strategy produced an orthogonally protected bifunctional chelator (BFC). The -NH2 group of the α-amino acid portion is Fmoc- and the -NH2 of Dap are Boc-protected. Fmoc-l-Lys(Dap(Boc)) was either conjugated to the N- and C-terminus of bombesin BBN(7-14) or integrated into the sequence using solid-phase peptide synthesis (SPPS). We also replaced the native lysine in a cyclic RGD peptide with l-Lys(Dap). For all peptides, quantitative labeling with the [99mTc(CO)3]+ core at a 10 μM concentration in PBS buffer (pH = 7.4) was achieved. For comparison, the rhenium homologues were prepared from [Re(OH2)3(CO) 3]+ and Lys(Dap)-BBN(7-14) or cyclo-(RGDyK(Dap)), respectively. Determination of integrin receptor binding showed low to medium nanomolar affinities for various receptor subtypes. The IC50 of cyclo-(RGDyK(Dap[Re(CO)3])) for αvβ3 is 7.1 nM as compared to 3.1 nM for nonligated RGD derivative. Biodistribution studies in M21 melanoma bearing nude mice showed reasonable α vβ3-integrin specific tumor uptake. Altogether, orthogonally protected l-Lys(Dap) represents a highly versatile building block for integration in any peptide sequence. Lys(Dap)-precursors allow high-yield 99mTc-labeling with [99mTc(OH2) 3(CO)3]+, forming small and hydrophilic complexes, which in turn leads to peptide radiopharmaceuticals with excellent in vivo characteristics.
Nonpeptidic propargylamines as inhibitors of lysine specific demethylase 1 (LSD1) with cellular activity
Schmitt, Martin L.,Hauser, Alexander-Thomas,Carlino, Luca,Pippel, Martin,Schulz-Fincke, Johannes,Metzger, Eric,Willmann, Dominica,Yiu, Teresa,Barton, Michelle,Schüle, Roland,Sippl, Wolfgang,Jung, Manfred
, p. 7334 - 7342 (2013/10/21)
Lysine demethylases play an important role in epigenetic regulation and thus in the development of diseases like cancer or neurodegenerative disorders. As the lysine specific demethylase 1 (LSD1/KDM1) has been strongly connected to androgen and estrogen dependent gene expression, it serves as a promising target for the therapy of hormone dependent cancer. Here, we report on the discovery of new small molecule inhibitors of LSD1 containing a propargylamine warhead, starting out from lysine containing substrate analogues. On the basis of these substrate mimicking inhibitors, we were able to increase potency by a combination of similarity-based virtual screening and subsequent synthetic optimization resulting in more druglike LSD1 inhibitors that led to histone hypermethylation in breast cancer cells.
Synthesis of (S)-gizzerosine, a potent inducer of gizzard erosion in chicks
Shimasaki, Yasuharu,Kiyota, Hiromasa,Sato, Minoru,Kuwahara, Shigefumi
, p. 9628 - 9634 (2007/10/03)
(S)-Gizzerosine, a potent inducer of gizzard erosion in chicks, was synthesized using successive zinc-mediated and palladium-catalyzed coupling reactions as the key steps.
Facile synthesis of (S)-gizzerosine - A potent inducer of gizzard erosion in chicks - Using successive zinc-mediated and palladium-catalyzed coupling reactions
Shimasaki, Yasuharu,Kiyota, Hiromasa,Sato, Minoru,Kuwahara, Shigefumi
, p. 3191 - 3192 (2007/10/03)
Gizzerosine, a potent inducer of gizzard erosion in chicks, was synthesized using successive inc-mediated and palladium-catalyzed coupling reactions as the key steps. The piperonyl moiety was used as a novel N-protecting group. Georg Thieme Verlag Stuttga
INDOLES, BENZIMIDAZOLES OR NAPHHIMIDAZOLES AS HISZONE DEACETYLASE (HDAC) INHIBITOR
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Page 80; 81, (2010/02/08)
A compound of the following formula (I):whereinR?1? is acyl, R?2? is hydrogen, orR?1? and R?2? are linked together to form a heterocyclic ring, R?5? is hydroxy, hydroxylamino, lower alkyl, lower alkoxy, halo(lower)alkyl or hydroxy(lower)alkyl, Q is lower
SYNTHESIS OF N-BENZYLOXYCARBONYL-L-α-AMINOADIPIC ACID, α-BENZYL ESTER
Baldwin, Jack E.,Killin, Stephen J.,Adlington, Robert M.,Spiegel, Udo
, p. 2633 - 2636 (2007/10/02)
A new synthesis of N-benzyloxycarbonyl-L-α-aminoadipic acid, α-benzyl ester (1) from L-lysine monohydrochloride (2) is reported.
SYNTHESIS OF THE RACEMIC AND OPTICALLY ACTIVE FORMS OF GIZZEROSINE, THE INDUCER OF GIZZARD EROSION IN CHICKS
Mori, Kenji,Sugai, Takeshi,Maeda, Yukari,Okazaki, Tomomi,Noguchi, Tadashi,Naito, Hiroshi
, p. 5307 - 5312 (2007/10/02)
The racemate end both the (R)- and (S)-forms of gizzerosine were synthesised, and the (S)-isomer was identified as the toxic substance in fish meal causing severe gizzard erosion (black vomit) in chicks.
Chemistry of Naturally Occurring Polyamines. 7. Selective Functionalization of Hydroxyputrescine
Tice, Colin M.,Ganem, Bruce
, p. 5043 - 5048 (2007/10/02)
As part of a program to synthesize biologically interesting polyamines and their conjugates, we report studies on the structure and reactivity of hydroxyputrescine-aldehyde adducts which permit regioselective functionalization of this rather rare naturall
Direct Preparation of α>-Diprotected L-α-Aminoadipic Acid from L-Lysine
Baldwin, Jack E.,Harrison, Paul,Murphy, John A.
, p. 818 - 819 (2007/10/02)
L-Lysine was converted into N-benzyloxycarbonyl-L-α-aminoadipic acid 1-benzyl ester by a short route which avoids the intermediacy of L-α-aminoadipic acid.
