1138-80-3Relevant articles and documents
Remarkable effects of donor esters on the α-chymotrypsin-catalyzed couplings of inherently poor amino acid substrates
Miyazawa, Toshifumi,Tanaka, Kayoko,Ensatsu, Eiichi,Yanagihara, Ryoji,Yamada, Takashi
, p. 997 - 1000 (1998)
The extremely low efficiency during the α-chymotrypsin-catalyzed coupling of an inherently poor amino acid substrate, e.g., alanine, using the methyl ester as an acyl donor was significantly improved using esters such as the 2,2,2-trifluoroethyl or carbamoylmethyl ester. The ameliorating effect of the latter ester was especially significant.
Photoinduced release of neurotransmitter amino acids from coumarin-fused julolidine ester cages
Piloto, Ana M.,Hungerford, Graham,Costa, Susana P. G.,Goncalves, M. Sameiro T.
, p. 7715 - 7723 (2013)
The photoinduced release of several neurotransmitter amino acids (glycine, alanine, glutamic acid, β-alanine and γ-aminobutyric acid) was accomplished from ester cages based on a new photoremovable protecting group consisting of a coumarin built on the julolidine nucleus, namely a (11-oxo-2,3,5,6,7,11-hexahydro-1H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-9-yl) methyl group. Photolysis and steady-state sensitization studies revealed that release of the active molecule occurred in short irradiation times at long wavelengths, with a very promising performance at 419 nm. Given the interest in the development of novel protecting groups that are cleavable with UV A or even visible radiation, it was found that a structural modification in the coumarin ring by assembly of a fused julolidine leads to a promising photolabile protecting group for organic synthesis and also for bioapplications. Photolysis and steady-state sensitization studies of several neurotransmitter amino acids from ester cages based on a new photoremovable protecting group consisting of a coumarin-fused julolidine nucleus, revealed that the release of the active molecule occurred in short irradiation times at long wavelengths, especially at 419 nm. Copyright
ACTION ON PEPTIDES BY WHEAT CARBOXYPEPTIDASE
Umetsu, H.,Ichishima, E.
, p. 591 - 592 (1983)
A kinetic analysis has been performed with purified wheat carboxypeptidase by the use of N-acyl dipeptides, Z-Gly-Pro-Leu-Gly (Z=benzyloxycarbonyl), angiotensin II and bradykinin.The values of kcat were dramatically influenced by amino acid residues occupying the penultimate position from the carbonyl terminus of substrates.The structure of the substrate did not appreciably affect the Km values. Key Word Index - Triticum aestivum; Gramineae; wheat; carboxypeptidase; peptides; kinetic parameters.
15N NMR Spectroscopy; 24-Chemical Shifts and Coupling Constants of α-Amino Acid N-Carboxyanhydrides and Related Heterocycles
Kricheldorf, Hans R.
, p. 198 - 203 (1980)
The chemical shifts of amino acid N-carboxyanhydrides (NCAs) and cyclic or linear urethanes are less sensitive to solvent effects than those of amides and lactams.The values of the one-bond 15N-1H coupling constants depend on the solvent and are 5-8 Hz larger than those of ureas and amides.The 15N-13C coupling constant of the N-CO group is also unusually high, while that of the N-CH group lies within the range known for N-acetylated aliphatic amines.The one-bond 15N-13C coupling constant was found to be insensitive to conformational changes.
First examples of bispidine-ferrocene cyclophanes
Churakov, A. V.,Gaisen, S. V.,Krut'ko, D. P.,Lemenovsky, D. A.,Medved'ko, A. V.,Minyaev, M. E.,Moiseeva, A. A.,Vatsadze, S. Z.,Wang, L.,Yu, H.
, (2021)
Two approaches for the syntheses of bispidine-ferrocene cyclophanes were reported. Both include the acylation of 1,5-dimethylbispidin-9-one (H2Bp) or its pendant amino-armed derivative by 1,1’-ferrocenoyl (Fc(CO)2) dichloride. The first approach allowed to isolate di-, tri- and pentameric cyclic oligomers of composition (BpFc(CO)2)n. The second one included the preliminary functionalization of H2Bp by N-protected glycine followed by deprotection and cyclization with Fc(COCl)2. The crystal structure of two new bispidine-ferrocene cyclophanes was established by single-crystal X-ray study. This study revealed the anti-conformation of amido-groups attached to the bispidine nitrogen atoms for both molecules. Various NMR techniques were applied to study the solution behavior of the macrocycles; the predominant anti-conformation in solution was also proved. The acyclic model compound Bp(FcCO)2 also showed only anti-conformer as revealed by VT-NMR and X-ray studies. Cyclic voltammetry study showed the difference in oxidation potentials of the Fc moiety within the row Bp(FcCO)2 – (BpFc(CO)2)2 – (BpFc(CO)2)3 with splitting of the oxidation curve in two later cases. The results obtained in this work will find an application in design and study of novel bispidine-ferrocene cyclophanes for the purposes of supramolecular sensing and catalysis.
Synthesis and In Vitro Neuroprotective Activity of Glycine Analogs of Gk-2 Dimeric Dipeptide Mimetic of Nerve Growth Factor 4th Loop
Antipov, P. I.,Antipova, T. A.,Firsova, Yu. N.,Gudasheva, T. A.,Nikolaev, S. V.,Rebeko, A. G.,Sazonova, N. M.,Tarasyuk, A. V.,Zvyagintsev, A. A.
, (2020/05/28)
A dimeric dipeptide mimetic of nerve growth factor (NGF), bis-(N-monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2), was previously developed at V. V. Zakusov State Institute of Pharmacology, activated specific TrkA receptors, and exhibited neuroprotective activity in vitro (10–5 – 10–9 M) and in vivo (0.1 – 10 mg/kg i.p. and p.o.). GK-2 was designed based on the beta-turn (-Asp94-Glu95-Lys96-Gln97-) of the NGF 4th loop and preserved the central dipeptide fragment (-Glu95-Lys96-). The Asp94 residue was replaced by its monosuccinyl bioisostere. The dimeric structure of NGF was reproduced using a bivalent hexamethylenediamine spacer. The structure—activity (neuroprotective) relationship for GK-2 was studied in the present work using a glycine scan, i.e., successive replacement of the peptide side groups by H. The bis-(N-acetyl-L-glutamyl-L-lysine) (GK-2Ac), bis-(N-monosuccinylglycyl-L-lysine) (GK-2-Gly1), and bis-(N-monosuccinyl-L-glutamylglycine) hexamethylenediamides (GK-2-Gly2) were less active with neuroprotective activity in vitro under oxidative stress for HT22 cells at concentrations 10 – 100 times greater than GK-2. The conclusion was drawn that each side radical of GK-2 was important for manifestation of the full neuroprotective activity of dimeric dipeptide GK-2, a mimetic of the NGF 4th loop. However, removal of any of the side radicals would probably not change the active structure of the beta-turn so that the two remaining side radicals should retain the ability to bind to their TrkA subsites. This could explain the retention of neuroprotective activity in the GK-2 glycine analogs.
Thiourea Modified Doxorubicin: A Perspective pH-Sensitive Prodrug
Krasnovskaya, Olga O.,Malinnikov, Vladislav M.,Dashkova, Natalia S.,Gerasimov, Vasily M.,Grishina, Irina V.,Kireev, Igor I.,Lavrushkina, Svetlana V.,Panchenko, Pavel A.,Zakharko, Marina A.,Ignatov, Pavel A.,Fedorova, Olga A.,Jonusauskas, Gediminas,Skvortsov, Dmitry A.,Kovalev, Sergey S.,Beloglazkina, Elena K.,Zyk, Nikolay V.,Majouga, Alexander G.
, p. 741 - 750 (2019/03/02)
A novel approach to the synthesis of pH-sensitive prodrugs has been proposed: thiourea drug modification. Resulting prodrugs can release the cytotoxic agent and the biologically active 2-thiohydantoin in the acidic environment of tumor cells. The concept of acid-catalyzed cyclization of thioureas to 2-thiohydantoins has been proven using a FRET model. Dual prodrugs of model azidothymidine, cytotoxic doxorubicin, and 2-thiohydantoin albutoin were obtained, which release the corresponding drugs in the acidic environment. The resulting doxorubicin prodrug was tested on prostate cancer cells and showed that the thiourea-modified prodrug is less cytotoxic (average IC50 ranging from 0.5584 to 0.9885 μM) than doxorubicin (IC50 ranging from 0.01258 to 0.02559 μM) in neutral pH 7.6 and has similar toxicity (average IC50 ranging from 0.4970 to 0.7994 μM) to doxorubicin (IC50 ranging from 0.2303 to 0.8110 μM) under mildly acidic conditions of cancer cells. Cellular and nuclear accumulation in PC3 tumor cells of Dox prodrug is much higher than accumulation of free doxorubicin.