116246-06-1Relevant academic research and scientific papers
Use of ozonolysis in the synthesis of C-terminal peptide aldehydes on solid support
Pothion, Catherine,Paris, Marielle,Heitz, Annie,Rocheblave, Luc,Rouch, Florence,Fehrentz, Jean-Alain,Martinez, Jean
, p. 7749 - 7752 (1997)
A new strategy for the synthesis of peptide aldehydes on solid support is presented. Reaction of a N-protected aminoaldehyde with caboethoxymethylene triphenylphosphorane yielded an α-β-unsaturated δ- amino derivative. After saponification, the resulting α-β-unsaturated δ- aminoacid was anchored to a solid support by an ester linkage (Merrifield resin) or by an amide linkage (MBHA, Expansin). After elongation of the peptide chain, ozonolysis yielded quite pure C-terminal peptide aldehydes in a good yield with no detectable racemization of the C-terminal residue.
Non-classical Helices with cis Carbon–Carbon Double Bonds in the Backbone: Structural Features of α,γ-Hybrid Peptide Foldamers
Ganesh Kumar, Mothukuri,Thombare, Varsha J.,Katariya, Mona M.,Veeresh, Kuruva,Raja, K. Muruga Poopathi,Gopi, Hosahudya N.
, p. 7847 - 7851 (2016)
The impact of geometrically constrained cis α,β-unsaturated γ-amino acids on the folding of α,γ-hybrid peptides was investigated. Structure analysis in single crystals and in solution revealed that the cis carbon–carbon double bonds can be accommodated into the 12-helix without deviation from the overall helical conformation. The helical structures are stabilized by 4→1 hydrogen bonding in a similar manner to the 12-helices of β-peptides and the 310helices of α-peptides. These results show that functional cis carbon–carbon double bonds can be accommodated into the backbone of helical peptides.
Consequence of Hapten Stereochemistry: An Efficacious Methamphetamine Vaccine
Olson, Margaret E.,Sugane, Takashi,Zhou, Bin,Janda, Kim D.
, p. 14089 - 14092 (2019/10/11)
Recent trends in methamphetamine (METH) misuse and overdose suggest society is inadvertently overlooking a brewing METH crisis. In the past decade, psychostimulant-related lethal overdoses and hospitalizations have skyrocketed 127 and 245%, respectively. Unlike the opioid crisis, no pharmaceutical interventions are available for treating METH use disorder or reversing overdose. Herein, we report the first active vaccine that offers protection from lethal (+)-METH challenge in male Swiss Webster mice. This vaccine formulation of (S)MLMH-TT adjuvanted with CpG ODN 1826 + alum successfully raised anti-METH antibodies in high titers, reduced (+)-METH distribution to the brain, and lowered (+)-METH-associated stereotypies in a hyperlocomotion assay. A comparison of enantiomeric haptens and the racemate elucidated the importance of employing (S)-stereochemistry in METH hapten design for optimal protection.
Synthesis of Enantiomerically Pure 3-Substituted Piperazine-2-acetic Acid Esters as Intermediates for Library Production
Reddy Guduru, Shiva Krishna,Chamakuri, Srinivas,Raji, Idris O.,MacKenzie, Kevin R.,Santini, Conrad,Young, Damian W.
, p. 11777 - 11793 (2018/09/27)
The piperazine heterocycle is broadly exploited in FDA-approved drugs and biologically active compounds, but its chemical diversity is usually limited to ring nitrogen substitutions, leaving the four carbon atoms underutilized. Using an efficient six-step synthesis, chiral amino acids were transformed into 3-substituted piperazine-2-acetic acid esters as diastereomeric mixtures whose cis and trans products (dr 0.56 a? 2.2:1, respectively) could be chromatographically separated. From five amino acids (both antipodes) was obtained a complete matrix of 20 monoprotected chiral 2,3-disubstituted piperazines, each as a single absolute stereoisomer, all but one in multigram quantities. In keeping with our overall purpose of constructing more Csp3-enriched compound libraries for drug discovery, these diverse and versatile piperazines can be functionalized on either nitrogen atom, allowing them to be used as scaffolds for parallel library synthesis and as intermediates for the production of novel piperazine compounds.
Synthesis and biological activity of cyclolinopeptide A analogues modified with γ4-bis(homo-phenylalanine)
J?drzejczak, Karol,Hrynczyszyn, Pawe?,Szczesio, Ma?gorzata,Artym, Jolanta,Jastrz?bek, Tomasz,Koci?ba, Maja,G?ówka, Marek,Huben, Krzysztof,Kochanowska, Iwona,Zimecki, Micha?,Zabrocki, Janusz,Jankowski, Stefan,Kolesińska, Beata
, p. 4265 - 4276 (2017/07/22)
Cyclolinopeptide A (CLA), an immunosuppressive nonapeptide derived from linen seeds, was modified with S or R-γ4-bis(homo-phenylalanine) in positions 3 or 4, or both 3 and 4. These modifications changed the flexibility of new analogues and distribution of intramolecular hydrogen bonds. Analogues 11 c(Pro1-Pro2-Phe3-S-γ4-hhPhe4-Leu5-Ile6-Ile7-Leu8-Val9), 13 c(Pro1-Pro2-S-γ4-hhPhe3-R-γ4-hhPhe4-Leu5-Ile6-Ile7-Leu8-Val9) and 15 c(Pro1-Pro2-R-γ4-hhPhe3-Phe4-Leu5-Ile6-Ile7-Leu8-Val9) existed as a mixture of stable cis/trans isomers of Pro-Pro peptide bond. The comparison of the relative spatial orientations in crystal state of the two carbonyl groups, neighboring γ-amino acids, revealed conformational similarities to α-peptides. The addition of two -CH2- groups in γ-amino acids led to a more rigid conformation, although a more flexible one was expected. A significant difference in the relative orientation of the carbonyl groups was found for cyclic γ-peptides with a dominance of an antiparallel arrangement. As carbonyl groups may be engaged in the interactions with plausible receptors through hydrogen bonds, a similar biological activity of the modified peptides was expected. Our biological studies showed that certain cyclic, but not the corresponding linear peptides, lowered the viability of peripheral blood mononuclear cells (PBMC) at 100?μg/mL concentration. The proliferation of PBMC induced by phytohemagglutinin A (PHA) was strongly inhibited by cyclic peptides only, in a dose-dependant manner. On the other hand, lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) production in whole blood cell cultures was inhibited by both linear and cyclic peptides. Peptide 15 c(Pro1-Pro2-R-γ4-hhPhe3-Phe4-Leu5-Ile6-Ile7-Leu8-Val9) blocked the expression of caspase-3, inhibited the expression of caspases-8 and -9 in 24?h culture of Jurkat cells, and caused DNA fragmentation in these cells, as an indicator of apoptosis. Thus, we revealed a new mechanism of immunosuppressive action of a nonapeptide.
Efficient synthesis of functionalized olefins by Wittig reaction using Amberlite resin as a mild base
Valkute, Tushar R.,Aratikatla, Eswar K.,Bhattacharya, Asish K.
, p. 581 - 589 (2017/03/15)
A convenient procedure for the synthesis of olefins by the reaction of stabilized, semistabilized, and nonstabilized phosphorous ylides with various aldehydes or ketone using Amberlite resin as a mild base is described. Our developed method offers facile and racemization-free synthesis of α,β-unsaturated amino esters and chiral allylic amine. The developed methodology offers mild reaction conditions, high efficiency, and facile isolation of the final products, a practical alternative to known procedures.
Structural features and molecular aggregations of designed triple-stranded β-sheets in single crystals
Bandyopadhyay, Anupam,Misra, Rajkumar,Gopi, Hosahudya N.
supporting information, p. 4938 - 4941 (2016/04/10)
Design, synthesis and single-crystal conformations of hybrid triple-stranded β-sheets composed of E-vinylogous residues are reported. Restricting conformational flexibility of β-strands through the insertion of carbon-carbon double bonds at facing positio
Engineering polypeptide folding through trans double bonds: Transformation of miniature β-meanders to hybrid helices
Ganesh Kumar, Mothukuri,Benke, Sushil N.,Poopathi Raja, K. Muruga,Gopi, Hosahudya N.
supporting information, p. 13397 - 13399 (2015/08/24)
Utilization of conjugated double bonds to engineer the novel folded miniature β-meander type structures, single step transformation of miniature β-meanders into ααγ4-hybrid peptide 10/12-helices using catalytic hydrogenation, their solution and single crystal conformations are reported.
A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition
Bera, Saurav,Panda, Gautam
, p. 3976 - 3985 (2014/06/09)
An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium-copper co-catalytic system has also been achieved in this work. The easy substrate availability and operational simplicity make the process suitable for further exploration. This journal is the Partner Organisations 2014.
Antiplasmodial activity of new 4-aminoquinoline derivatives against chloroquine resistant strain
Sinha, Manish,Dola, Vasanth R.,Agarwal, Pooja,Srivastava, Kumkum,Haq, Wahajul,Puri, Sunil K.,Katti, Seturam B.
, p. 3573 - 3586 (2014/07/07)
Emergence and spread of multidrug resistant strains of Plasmodium falciparum has severely limited the antimalarial chemotherapeutic options. In order to overcome the obstacle, a set of new side-chain modified 4-aminoquinolines were synthesized and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum. The key feature of the designed molecules is the use of methylpiperazine linked α, β3- and γ-amino acids to generate novel side chain modified 4-aminoquinoline analogues. Among the evaluated compounds, 20c and 30 were found more potent than CQ against K1 and displayed a four-fold and a three-fold higher activity respectively, with a good selectivity index (SI = 5846 and 11,350). All synthesized compounds had resistance index between 1.06 and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that this series of compounds act on heme polymerization target.
