3845-64-5Relevant articles and documents
Synthesis and X-ray Structure of the Chiral, Polydentate Cation Binder N--L-methionyl>histamine
Modder, Johan F.,Vrieze, Kees,Spek, Anthony L.,Koten, Gerard van
, p. 5606 - 5610 (1991)
A synthetic route has been developed to obtain N--L-methionyl>histamine, optically pure (α20 = -8.13 deg/L mol-1 dm-1), from a sequence of reactions involving L-methionine, histamine, and 5-methyl-2-thiophenecarbaldehyde.The described procedure affords gram quantities in an overall yield of 40percent, without the need of any chromatographic techniques.Moreover, the removal of the well-known tert-butyloxycarbonyl amino-protection group (BOC) with gaseous hydrochloric acid, in the present synthesis, had considerable advantages compared with the commonly applied trifluoroacetic acid method.The structure of N--L-methionyl>histamine in the solid has been determined by X-ray diffraction techniques.C16H22N4OS2 crystallizes in the monoclinic space group P21, with a = 5.233(1), b = 9.556(1), and c = 17.919(1) Angstroem; β = 98.32(1) deg; and Z = 2.Noteworthy aspects of the tertiary structure of the molecule are the fact that it is almost flat, the three arms connected to methionine-Ca, being the (thienylmethylidene)amino moiety, the "imidazole-amide" fragment, and the methionine side chain, spread out. ?-Conjugation causes the (thienylmethylidene)amino moiety to have a planar s-cis conformation, and the methionine side chain's all-trans conformation is due to vicinal interactions.The gauche conformation of the "imidazole-amide" does not have a clear origin, but is no artifact of the solid state.Intra- and intermolecular hydrogen bonds are prominently present, the former determining the relative orientations of the aforementioned arms and the latter linking the title molecules into two-dimensional, sheetlike entities.
Synthesis of pyrimidine nucleoside and amino acid conjugates
Koplūnait?, Martyna,Butkut?, Kamil?,Me?kys, Rolandas,Taurait?, Daiva
supporting information, (2020/11/13)
The synthesis of novel pyrimidine nucleoside bioconjugates with amino acids is presented. The N4-amino acid-acylated 2′-deoxycytidine analogues, modified with various amino acids, were synthesized using a three-step synthesis and obtained in moderate overall yields. Novel amino acid-alkylated 2′-deoxycytidine derivatives were obtained during the rearrangement of amino acid-acylated derivatives that occurred during Boc deprotection.
DIPEPTIDE MIMETICS OF NGF AND BDNF NEUROTROPHINS
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Paragraph 0188, (2019/04/16)
The invention relates to compounds having either agonist or antagonist activities for the neurotrophins NGF and BDNF and represented by monomeric or dimeric substituted dipeptides that are analogs of the exposed portions of loop 1 or loop 4 regions of these neurotrophins near or at a beta-turn of the respective loop. N-acylated substituents of these dipeptides are biostereoisomers of the amino acid residues preceding these dipeptide sequences in the neurotrophin primary structure. The dimeric structure is produced advantageously by using hexatnethylenediaanine to which dipeptides are attached via their carboxyl groups. The claimed compounds displayed neuroprotective and differentiation-inducing activities in cellular models and enhanced the amount of phosphorylated tyrosine kinase A and the heat shock proteins Hsp32 and Hsp70 in the concentration range of 10 -9 to 10 -5 M. They also displayed neuroprotective, anti-parkinsonian, anti-stroke, anti-ischemic, anti-depressant and anti-amnestic activities in animal models and were active in experimental models of Alzheimer's disease. These in vivo effects of the claimed compounds are displayed in the dose range of 0.01 to 10 mg/kg when administered intraperitoneally.
Ynamide-Mediated Thiopeptide Synthesis
Yang, Jinhua,Wang, Changliu,Xu, Silin,Zhao, Junfeng
supporting information, p. 1382 - 1386 (2019/01/08)
Exploration of the full potential of thioamide substitution as a tool in the chemical biology of peptides and proteins has been hampered by insufficient synthetic strategies for the site-specific introduction of a thioamide bond into a peptide backbone. A novel ynamide-mediated two-step strategy for thiopeptide bond formation with readily available monothiocarboxylic acids as thioacyl donors is described. The α-thioacyloxyenamide intermediates formed from the ynamides and monothiocarboxylic acids can be purified, characterized, and stored. The balance between their activity and stability enables them to act as effective thioacylating reagents to afford thiopeptide bonds under mild reaction conditions. Amino acid functional groups such as OH, CONH2, and indole NH groups need not be protected during thiopeptide synthesis. The modular nature of this strategy enables the site-specific incorporation of a thioamide bond into peptide backbones in both solution and the solid phase.
Solventless mechanosynthesis of N-protected amino esters
Konnert, Laure,Lamaty, Frederic,Martinez, Jean,Colacino, Evelina
, p. 4008 - 4017 (2014/05/20)
Mechanochemical derivatizations of N- or C-protected amino acids were performed in a ball mill under solvent-free conditions. A vibrational ball mill was used for the preparation of N-protected α- and β-amino esters starting from the corresponding N-unmasked precursors via a carbamoylation reaction in the presence of di-tert-butyl dicarbonate (Boc2O), benzyl chloroformate (Z-Cl) or 9-fluorenylmethoxycarbonyl chloroformate (Fmoc-Cl). A planetary ball mill proved to be more suitable for the synthesis of amino esters from N-protected amino acids via a one-pot activation/esterification reaction in the presence of various dialkyl dicarbonates or chloroformates. The spot-to-spot reactions were straightforward, leading to the final products in reduced reaction times with improved yields and simplified work-up procedures.
Transformation of gold(I)-cyclo[-Met-Met-] complex supramolecular fibers into aligned gold nanoparticles
Furutani, Masahiro,Kudo, Kazuaki
supporting information, p. 601 - 603 (2013/07/27)
A cyclic dipeptide cyclo[L-methionylL- methionyl] and gold(I) cation were found to form a complex in a 1:2 ratio. Pouring a DMF solution of the complex into ethyl acetate afforded fibers with lengths of more than 20 μm and 100400nm in width, which consisted of fibrous nanostructures 50100nm in diameter. Treatment of this supramolecular fiber with catechol gave linearly aligned Au nanoparticles on the original fibers.
Amino acid and peptide synthesis and functionalization by the reaction of thioacids with 2,4-dinitrobenzenesulfonamides
Crich, David,Sana, Kasinath,Guo, Songpo
, p. 4423 - 4426 (2008/03/12)
(Formula Presented) Readily prepared amino thioacids react at room temperature in DMF in the presence of cesium carbonate with 2,4- dinitrobenzenesulfonamides to give amides. When the sulfonamide is derived from an amino acid the method results in peptide bond formation, whereas the use of carbohydrate derived sulfonamides gives neoglycoconjugates.
New prolyl oligopeptidase inhibitors developed from dicarboxylic acid bis(L-prolyl-pyrrolidine) amides
Wallén, Erik A. A.,Christiaans, Johannes A. M.,Jarho, Elina M.,Forsberg, Markus M.,Ven?l?inen, Jarkko I.,M?nnist?, Pekka T.,Gynther, Jukka
, p. 4543 - 4551 (2007/10/03)
Isophthalic acid bis(L-prolyl-pyrrolidine) amide is a very potent prolyl oligopeptidase inhibitor, but it has a log P value of -0.2, which is very low for a compound targeted to the brain. Therefore, these types of compounds were further modified to improve the structure-activity relationships, with the focus on increasing the log P value. The inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. The most promising compounds resulted from replacing the pyrrolidinyl group at the P5 site by cycloalkyl groups, such as cyclopentyl and cyclohexyl groups, and by a phenyl group. These compounds are slightly more potent, and they have a significantly higher log P value. The potency of these compounds was further increased by replacing the pyrrolidinyl group at the P1 site by 2(S)-cyanopyrrolidinyl and 2(S)-(hydroxyacetyl)pyrrolidinyl groups.
Met-Ile-Phe-Leu derivatives: Full and partial agonists of human neutrophil formylpeptide receptors
Dalpiaz, Alessandro,Scatturin, Angelo,Vertuani, Gianni,Pecoraro, Rita,Borea, Pier Andrea,Varani, Katia,Traniello, Serena,Spisani, Susanna
, p. 327 - 333 (2007/10/03)
The biological action of a series of Met-Ile-Phe-Leu analogues was analyzed on human neutrophils, to evaluate their ability to interact with formylpeptide receptors and to induce the related neutrophil responses. Three in vitro assays were carried out: receptor binding, chemotaxis and superoxide anion release. Our results demonstrate that formyl-Met-Ile-Phe-Leu derivatives act as more potent full agonists than formyl-Met-Leu-Phe, the tripeptide normally used as a model chemoattractant for the study of cell functions. On the other hand, the presence of N-ureidoisopropyl substituent in tetrapeptides imparts weak partial agonist properties. It has furthermore been demonstrated that the C-terminal methyl esterification or amination weakly influences the properties of tetrapeptide homologues. Finally, t-Boc-Met-Ile-Phe-Leu derivatives do not appear able to interact with formylpeptide receptors.
Synthesis of functional ras lipoproteins and fluorescent derivatives
Kuhn,Owen,Bader,Wittinghofer,Kuhlmann,Waldmann
, p. 1023 - 1035 (2007/10/03)
For the study of biological signal transduction, access to correctly lipidated proteins is of utmost importance. Furthermore, access to bioconjugates that embody the correct structure of the protein but that may additionally carry different lipid groups or labels (i.e., fluorescent tags) by which the protein can be traced in biological systems, could provide invaluable reagents. We report here of the development of techniques for the synthesis of a series of modified Ras proteins. These modified Ras proteins carry a number of different, natural and non-natural lipid residues, and the process was extended to also provide access to a number of fluorescently labeled derivatives. The maleimide group provided the key to link chemically synthesized lipopeptide molecules in a specific and efficient manner to a truncated form of the H-Ras protein. Furthermore, a preliminary study on the biological activity of the natural Ras protein derivative (containing the normal farnesyl and palmitoyl lipid residues) has shown full biological activity. This result highlights the usefulness of these compounds as invaluable tools for the study of Ras signal transduction processes and the plasma membrane localization of the Ras proteins.
