- GRANZYME B DIRECTED IMAGING AND THERAPY
-
Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
- -
-
Page/Page column 82; 105
(2019/09/04)
-
- Synthesis of structural analogues of GGT1-DU40, a potent GGTase-1 inhibitor
-
A series of new substituted pyrazoles 2-12 have been synthesized. The synthesized compounds are structural analogues of GGT1-DU40 1, a highly potent and selective inhibitor of protein geranylgeranyltransferase I (GGTase-I) both in vitro and in vivo. The i
- Mansha, Muhammad,Ullah, Nisar,Alhooshani, Khalid
-
p. 333 - 344
(2016/04/26)
-
- Pyrazole-based potent inhibitors of GGT1: Synthesis, biological evaluation, and molecular docking studies
-
In this study, a series of pyrazole-based structural analogues of GGTI-DU40 (1) have been synthesized and biologically evaluated for geranylgeranyltransferase 1 (GGT1) and farnesyltransferase (FT) inhibition. The screening results revealed that 2 (IC50?=?2.4?μM) and 5 (IC50?=?3.1?μM) are potent GGT1 inhibitors (GGTIs), possessing higher inhibitory activity compared to the control compound 1 (IC50?=?3.3?μM). The anti-proliferative efficacy of these compounds was further assayed against MDA-MB-231?cells which indicated a significantly higher activity of 2 (IC50?=?7.6?μM) compared to 1 (IC50?=?23.0?μM). To examine the capacity of the synthesized compounds to inhibit GGT1 in an intact cell, western blot analysis was performed on the MDA-MB-231?cell line, which revealed very high inhibitory cellular activity of 2 and 5 and demonstrated their capacity to inhibit prenylation of endogenous proteins. Molecular docking studies of 2 against the crystal structure of GGT1 complexed with a geranylgeranyl pyrophosphate (GGPP) Analog and a CaaX (C?=?cysteine, aa?=?aliphatic amino acids, and X?=?any amino acid) portion of the KKKSKTKCVIL peptide substrate revealed several hydrogen bonding interactions and π-π contacts between 2 and the binding pocket of GGT1. Together these data suggest that compound 2 could proceed to in?vivo investigation to further assess its efficacy and cytotoxicity.
- Mansha, Muhammad,Kumari, Udayappan Udhaya,Cournia, Zoe,Ullah, Nisar
-
p. 666 - 676
(2016/09/14)
-
- Electron-donating and rigid p-stereogenic bisphospholane ligands for highly enantioselective rhodium-catalyzed asymmetric hydrogenations
-
More electron donating, more rigid: A new highly electron-donating P-stereogenic bisphospholane ligand (ZhangPhos) was synthesized in a practical and highly enantioselective manner from a commercially available chiral source. Better or comparable enantioselectivities and reactivities than TangPhos were achieved in rhodium-catalyzed hydrogenation of various functionalized olefins (see scheme; nbd=3,5-norbornadiene). Copyright
- Zhang, Xiaowei,Huang, Kexuan,Hou, Guohua,Cao, Bonan,Zhang, Xumu
-
supporting information; experimental part
p. 6421 - 6424
(2010/12/19)
-
- Resolution of N-protected amino acid esters using whole cells of Candida parapsilosis ATCC 7330
-
Whole cells of Candida parapsilosis ATCC 7330 were used for the resolution of N-acetyl amino acid esters. Excellent enantioselectivities (E = 40 to >500) were achieved for the resolution of N-protected protein and non-protein amino acid esters giving good yields (28-50%) and high enantiomeric excesses (up to >99%) for both enantiomers.
- Stella, Selvaraj,Chadha, Anju
-
experimental part
p. 457 - 460
(2010/06/21)
-
- Novel atropisomeric bisphosphine ligands with a bridge across the 5,5′-position of the biphenyl for asymmetric catalysis
-
A new type of atropisomeric bisphosphine ligand 2 with a bridge across the 5,5′-position of the biphenyl has been developed. The axial chirality of this type of ligands can be retained by macrocyclic ring strain produced from 5,5′-linkage of the biphenyl
- Wei, Hao,Zhang, Yong Jian,Wang, Feijun,Zhang, Wanbin
-
p. 482 - 488
(2008/09/19)
-
- Synthesis of a novel spiro bisphosphinite ligand and its application in Rh-catalyzed asymmetric hydrogenation
-
A novel, chiral bisphosphinite ligand (R)-SpiroBIP has been synthesized. The rhodium complex of the ligand was found to be highly enantioselective in the asymmetric hydrogenation of α-dehydroamino acid derivatives.
- Guo, Zhenqiu,Guan, Xiaoyu,Chen, Zhiyong
-
p. 468 - 473
(2007/10/03)
-
- Asymmetric catalysis based on chiral phospholanes and hydroxyl phospholanes
-
Chiral phosphine ligands derived from chiral natural products including D-mannitol and tartaric acid. The ligands contain one or more 5-membered phospholane rings with multiple chiral centers, and provide high stereoselectivity in asymmetric reactions.
- -
-
Page column 22
(2010/02/06)
-
- Monodentate Phosphoramidites: A Breakthrough in Rhodium-Catalysed Asymmetric Hydrogenation of Olefins
-
Monodentate phosphoramidites based on BINOL or substituted BINOL are excellent ligands for the rhodium-catalysed asymmetric hydrogenation of olefins. Very high enantioselectivities were obtained with MonoPhos (7a) the simplest member of this class, a ligand that is prepared in a single step from BINOL and HMPT. Turnover numbers up to 6000 have been obtained in the hydrogenation of dehydroamino acid derivatives. Enantioselectivities in the hydrogenation of dehydroamino acids are solvent dependent; in non-protic solvents they range from 95-99%. Itaconic acid and its dimethyl ester could be hydrogenated with 96 and 94% e.e., respectively. Hydrogenation of aromatic enamides gave the corresponding acylated amines in 86-94% e.e. Several analogous phosphoramidite ligands have been pre-pared. Surprisingly, bidentate ligands gave poorer results, both in terms of rate as well as enantioselectivity. Taddol-based phosphoramidites led to poor e.e. and slow rates. Methyl substituents at the 3,3′-position of BINOL led to a sharply reduced rate and a somewhat lower enantioselectivity. Bromo substituents at the 6,6′-position led to a slightly reduced rate but little effect was seen on enantioselectivity. Use of octahydro-MonoPhos (11) gave results that were very similar to those obtained with 7a. The rate of the reaction is dependent on the hydrogen pressure, however, the enantioselectivity is not affected. The rate of the dehydroamino acid hydrogenation also increases if the ligand to rhodium ratio is reduced from 2.2 to 1.5 or even to 1.0; yet, there is no deleterious effect on the enantioselectivity. Catalytic activity ceases with L/Rh = 3 when dehydroamino acid derivatives were used as substrate. The reaction shows a positive non-linear effect, which confirms the presence of Rh-complexes with more than one ligand. Following the hydrogenation of methyl 2-acetamidocinnnamate with Rh(nbd)2BF4/7a by electrospray mass spectrometry showed the presence of several rhodium species. Notable are the presence of [Rh(7a)]3+ and [Rh(7a)]4+. There is at present insufficient evidence to conclude if the active catalytic species carries one or two ligands. In view of the low cost of MonoPhos this invention might well lead to a broader application of asymmetric olefin hydrogenation for the production of enantiopure amino acids and amines.
- Van Den Berg, Michel,Minnaard, Adriaan J.,Haak, Robert M.,Leeman, Michel,Schudde, Ebe P.,Meetsma, Auke,Feringa, Ben L.,De Vries, André H. M.,Maljaars, C. Elizabeth P.,Willans, Charlotte E.,Hyett, David,Boogers, Jeroen A. F.,Henderickx, Hubertus J. W.,De Vries, Johannes G.
-
p. 308 - 323
(2007/10/03)
-
- Acylase I catalysed hydrolysis of para-substituted (S)-phenylalanine derivatives from mixtures of the racemic ortho- and para-substituted isomers
-
para-Substituted (S)-phenylalanines may be obtained by treatment of the corresponding mixtures of ortho- and para-substituted N-acetyl-(RS)- phenylalanines with Acylase I from porcine kidney. The selectivity of the enzyme may be attributed to its evolution to digest peptide derivatives of (S)-phenylalanine and (S)-tyrosine.
- Easton, Christopher J.,Harper, Jason B.
-
p. 5269 - 5272
(2007/10/03)
-
- Synthesis of (S)-3,4-dihydroxyphenylalanine (L-DOPA) and unnatural α-amino acids via enzymatic resolution using alcalase
-
Enzymatic resolution has been used for the synthesis of L-DOPA with high optical purity.N-Acetyl-(R,S)-3,4-methylenedioxyphenylalanine methyl ester (2b) on enzymatic resolution by alcalase (Subtilisin Carlsberg) yields N-acetyl-(S)-3,4-methylenedioxyphenylalanine (3b) which upon acid treatment affords (S)-3,4-dihydroxyphenylalanine (L-DOPA) (4).Several optically active unnatural N-acetylated and N-benzoylated α-amino acids have been prepared by similar enzymatic resolution.
- Tyagi, O D,Boll, P M,Parmar, V S,Taneja, Poonam,Singh, S K
-
p. 851 - 854
(2007/10/02)
-
- BIOCATALYTICAL TRANSFORMATIONS II. ENANTIOSELECTIVE HYDROLYSIS OF N-ACETYL-FLUORO-PHENYLALANINE-ETHYLESTERS BY LYOPHILISED YEAST
-
The three nuclear substituted monofluoro D-N-acetylphenylalanine-ethylesters were obtained in excellent yield via enantioselective hydrolysis of their respective racemates by use of lyophilised yeast (Saccharomyces cerevisiae Hansen).
- Csuk, Rene,Glaenzer, Brigitte I.
-
-