63984-03-2Relevant articles and documents
SUBSTITUTED 2,3-BENZODIAZEPINES DERIVATIVES
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Page/Page column 53, (2021/08/06)
Derivatives of 2,3- benzodiazepines as inhibitors of Bromodomain and extra C-terminal domain (BET) proteins, in particular the BRD4 family member, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceuti
Optimized reaction pair of the Cyshis tag and Ni(II)-Nta probe for highly selective chemical labeling of membrane proteins
Zenmyo, Naoki,Tokumaru, Hiroki,Uchinomiya, Shohei,Fuchida, Hirokazu,Tabata, Shigekazu,Hamachi, Itaru,Shigemoto, Ryuichi,Ojida, Akio
supporting information, p. 995 - 1000 (2019/07/18)
Chemical labeling of proteins with synthetic molecular probes offers the possibility to probe the functions of proteins of interest in living cells. However, the methods for covalently labeling targeted proteins using complementary peptide tag-probe pairs are still limited, irrespective of the versatility of such pairs in biological research. Herein, we report the new CysHis tag-Ni(II) probe pair for the specific covalent labeling of proteins. A broad-range evaluation of the reactivity profiles of the probe and the CysHis peptide tag afforded a tag-probe pair with an optimized and high labeling selectivity and reactivity. In particular, the labeling specificity of this pair was notably improved compared to the previously reported one. This pair was successfully utilized for the fluorescence imaging of membrane proteins on the surfaces of living cells, demonstrating its potential utility in biological research.
Heterovalent inhibitors targeting N-end Rule Pathway and its use
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, (2016/10/10)
An alkali-soluble polymer resin compound of formula 1 a including N-end Rule pathway inhibitors disclosure the composition. According to type 1 and type 2 herein each compounds recognizing substrate UBR box and a ClpS box a mammal having two tolerance N-e
Synthesis and self-association properties of flexible guanidiniocarbonylpyrrole-carboxylate zwitterions in DMSO: Intra- versus intermolecular ion pairing
Schmuck, Carsten,Rehm, Thomas,Geiger, Lars,Schaefer, Mathias
, p. 6162 - 6170 (2008/02/10)
(Chemical Equation Presented) We have synthesized a new class of flexible zwitterions 6a-e, in which a carboxylate is linked via an alkyl chain with variable length (one to five methylene groups) to a guanidiniocarbonylpyrrole cation. The self-association properties of these zwitterions were determined by NMR dilution studies in DMSO and by ESI-MS experiments. The stability and hence also the size of the aggregates formed via self-assembly is critically dependent on the length and therefore flexibility of the spacer. Whereas the smallest zwitterion 6a forms large aggregates already at low concentrations, the more flexible zwitterions only form small oligomers (6b) or dimers (6c-e) at much larger concentrations. The differences between the five zwitterions can be explained based on the different extent of intramolecular ion pairing within the monomers. Any intramolecular ion pairing, which becomes possible with increasing linker length, stabilizes the monomer and therefore destabilizes any oligomer.
Building Units for N-Backbone Cyclic Peptides. 3. Synthesis of Protected Nα-(ω-Aminoalkyl)amino Acids and Nα-(ω-Carboxyalkyl)amino Acids
Muller, Dan,Zeltser, Irena,Bitan, Gal,Gilon, Chaim
, p. 411 - 416 (2007/10/03)
An improved synthesis of a family of amino acids that contain ω-aminoalkyl groups and of a new family containing ω-carboxyalkyl groups linked to the α-amine is described. The synthesis was performed by alkylation of suitably monoprotected alkylenediamines and protected ω-amino acids with triflates of α-hydroxy acid esters. The reaction proceeded with inversion of configuration yielding optically pure products. The Nα-(ω-aminoalkyl)amino acids and Nα-(ω-carboxyalkyl)amino acids were orthogonally protected to allow their incorporation into peptides by solid-phase peptide synthesis (SPPS) methodology.
New kelatorphan-related inhibitors of enkephalin metabolism: Improved antinociceptive properties
Xie,Soleilhac,Schmidt,Peyroux,Roques,Fournie-Zaluski
, p. 1497 - 1503 (2007/10/02)
In order to improve the in vivo protection of enkephalins from enzymatic degradation, a new series of inhibitors derived from kelatorphan [HONHCOCH2CH(CH2Ph)CONHCH(CH3)COOH], the first-described complete inhibitor of enkephalin metabolism, were designed by modification of the C-terminal amino acid. The progressive lengthening of the chain of this residue shows that a β-alanine seems to be the best basic model for the conception of such types of compounds. On the other hand, the methylation of the amide bond, which is well accepted by aminopeptidase N (EC 3.4.11.2) and dipeptidylaminopeptidase, induced a significant loss of affinity for neutral endopeptidase -24.11. Starting from these data, compounds containing a variously substituted β-alanine residue and corresponding to the general formula HONHCOCH2CH(CH2Ph)CONHCH(R1)CH(R2)COOH were synthesized. All these molecules inhibit neutral endopeptidase -24.11 and dipeptidylaminopeptidase in the nanomolar range, and those containing an aromatic chain (compound 7A, R1 = CH2Ph,R2 = H, and compound 8A, R1 = Ph, R2 = H) inhibit the biologically relevant aminopeptidase N, with IC50's around 10-8 M. Intracerebroventricular injection in mice of these multienzyme inhibitors produced an efficient and naloxone-reversible analgesic response (hot plate test): compounds 7A and 8A were shown to be more potent than kelatorpohan in increasing the jump latency time, in agreement with their in vitro properties, and these new compounds were found to increase the forepaw lick latency, a reflex considered as a typical morphine response.
SUBSTITUTED 5-AMINO-4-HYDROXYVALERYL DERIVATIVES
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, (2008/06/13)
Compounds of the formula STR1 in which R 1 represents hydrogen or acyl, X 1 represents an optionally N-alkylated amino acid residue that is bonded N-terminally to R 1 and C-terminally to X 2, X 2 represents an optionally N-alkylated amino acid residue tha
Antibacterial halogenoacetyl derivatives of amino acids and simple peptides
Goodacre,Jeffries,Nayler,Ponsford,Stirling
, p. 1445 - 1448 (2007/10/12)
The vital role of D-alanine and L-lysine in the peptidoglycan crosslinking process in the bacterial cell wall prompted preparation of various small peptides incorporating these amino acids. N-Iodoacetyl or -bromoacetyl derivatives of the peptides were then prepared in the hope that they would serve as active-site-directed irreversible inhibitors of cell wall transpeptidases. Certain of the halogenoacetyl dipeptide esters, but not the corresponding free acids, showed slight antistaphylococcal activity. Subsequent structural variation showed that inclusion of D-alanine or L-lysine was not necessary, since antibacterial activity was at least as good when the dipeptide unit was replaced by glycylglycine or by an ω-aminoalkanoic acid. It was concluded that the observed antibacterial activity was probably not due to specific inhibition of a cell wall transpeptidase.