146549-21-5Relevant articles and documents
Novel design of bicyclic β-turn dipeptides on solid-phase supports and synthesis of [3.3.0]-bicyclo[2,3]-leu-enkephalin analogues
Gu, Xuyuan,Ying, Jinfa,Agnes, Richard S.,Navratilova, Edita,Davis, Peg,Stahl, Gannon,Porreca, Frank,Yamamura, Henry I.,Hruby, Victor J.
, p. 3285 - 3288 (2004)
(Chemical Equation Presented) External bicyclic β-turn dipeptide mimetics provide an excellent design approach that can offer a rich chiral ensemble of structures with different backbone conformations. We report herein a novel design of a convergent combinatorial synthetic methodology, which is illustrated by the solid-phase synthesis of a series of [3.3.0]-bicyclo [2,3]-Leu-enkephalin analogues. The reactions were optimized and the epimeric configurations were determined by 2D NMR spectroscopy. Biological assays show that these analogues have more potent δ binding affinity and bioactivity for δ vs μ opioid receptor, which may be related to the different conformations preferred by these analogues in our modeling studies.
Development of solid-supported methodology for the preparation of peptidoglycan fragments containing (2S,6R)-diaminopimelic acid
Simon, Justine F.,Lamborelle, Nicolas,Zervosen, Astrid,Lemaire, Christian,Joris, Bernard,Luxen, André
, p. 1572 - 1575 (2016)
Herein, we describe the development of an efficient solid-supported methodology for the stereoselective synthesis of two peptides containing (2S,6R)-diaminopimelic acid, (S)-Ala-γ-(R)-Glu-(2S,6R)-A2pm-(R)-Ala 1 and γ-(R)-Glu-(2S,6R)-A2pm 2. The platform consists of a Wang resin anchored by an amino acid chain including allylglycine. By olefin cross metathesis with vinylglycine, unsaturated protected (2S,6R)-A2pm was fixed on solid support. Peptides were achieved by cleavage of cross metathesis products from resin, followed by reduction of double bonds along removing of protecting groups. Furthermore, this efficient solid phase approach will lead to peptide and muropeptide libraries.
Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
supporting information, p. 8297 - 8302 (2021/03/01)
Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
Macrocyclic BACE1 inhibitors with hydrophobic cross-linked structures: Optimization of ring size and ring structure
Otani, Takuya,Hattori, Yasunao,Akaji, Kenichi,Kobayashi, Kazuya
, (2021/11/22)
Based on the X-ray crystallography of recombinant BACE1 and a hydroxyethylamine-type peptidic inhibitor, we introduced a cross-linked structure between the P1 and P3 side chains of the inhibitor to enhance its inhibitory activity. The P1 and P3 fragments bearing terminal alkenes were synthesized, and a ring-closing metathesis of these alkenes was used to construct the cross-linked structure. Evaluation of ring size using P1 and P3 fragments with various side chain lengths revealed that 13-membered rings were optimal, although their activity was reduced compared to that of the parent compound. Furthermore, the optimal ring structure was found to be a macrocycle with a dimethyl branched substituent at the P3 β-position, which was approximately 100-fold more active than the non-substituted macrocycle. In addition, the introduction of a 4-carboxymethylphenyl group at the P1′ position further improved the activity.
Divergent Access to Histone Deacetylase Inhibitory Cyclopeptides via a Late-Stage Cyclopropane Ring Cleavage Strategy. Short Synthesis of Chlamydocin
Elek, Gábor Zoltán,Koppel, Kaur,Zubrytski, Dzmitry M.,Konrad, Nele,J?rving, Ivar,Lopp, Margus,Kananovich, Dzmitry G.
supporting information, p. 8473 - 8478 (2019/10/16)
A unified step-economical strategy for accessing histone deacetylase inhibitory peptides is proposed, based on the late-stage installation of multiple zinc-binding functionalities via the cleavage of the strained cyclopropane ring in the common pluripoten
Methods for the synthesis of dicarba bridges in organic compounds
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Page/Page column 151, (2015/11/17)
The present invention relates to methods for forming dicarba bridges in organic compounds. This involves the use of a pair of complementary metathesisable groups on the organic compound, and subjecting the compound to cross-metathesis under microwave radiation conditions. In an alternative, the compounds contain a turn-inducing group between the pair of cross-metathesisable groups to facilitate the cross-metathesis.
Insight into Transannular Cyclization Reactions to Synthesize Azabicyclo[X.Y.Z]alkanone Amino Acid Derivatives from 8-, 9-, and 10-Membered Macrocyclic Dipeptide Lactams
Atmuri, N. D. Prasad,Lubell, William D.
, p. 4904 - 4918 (2015/06/02)
An efficient method for synthesizing different functionalized azabicyclo[X.Y.0]alkanone amino acid derivatives has been developed employing electrophilic transannular cyclizations of 8-, 9-, and 10-membered unsaturated macrocycles to form 5,5-, 6,5-, 7,5-, and 6,6-fused bicylic amino acids, respectively. Macrocycles were obtained by a sequence featuring peptide coupling of vinyl-, allyl-, homoallyl-, and homohomoallylglycine building blocks followed by ring-closing metathesis. X-ray crystallographic analyses of the 8-, 9-, and 10-membered macrocyclic lactam starting materials as well as certain bicyclic amino acid products provided insight into their conformational preferences as well as the mechanism for the diastereoselective formation of specific azabicycloalkanone amino acids by way of transannular iodolactamization reactions. (Chemical Equation Presented).
Influence of α-methylation in constructing stapled peptides with olefin metathesis
Zhang, Qingzhou,Shi, Xiaodong,Jiang, Yanhong,Li, Zigang
, p. 7621 - 7626 (2014/12/11)
Ring-closing metathesis is commonly utilized in peptide macro-cyclization. The influence of α-methylation of the amino acids bearing the olefin moieties has never been systematically studied. In this report, controlled reactions unambiguously indicate that α-methylation at the N-terminus of the metathesis sites is crucial for this reaction to occur. Also, we first elucidated that the E-isomers of stapled peptides are significantly more helical than the Z-isomers.
Synthesis of conformationally constrained γ-d-glutamyl-meso- diaminopimelic acid derivatives as ligands of nucleotide-binding oligomerization domain protein 1 (Nod1)
Jakopin, ?iga,Gobec, Martina,Kodela, Jaka,Hazdovac, Toni,Mlinari?-Ra??an, Irena,Sollner Dolenc, Marija
, p. 232 - 243 (2013/10/01)
Nod1, an important member of the pattern recognition receptor family, remains a virtually unexploited target. Harnessing its innate immune stimulatory properties still remains an unfulfilled goal of medicinal chemistry. Nucleotide-binding oligomerization domain protein 1 (Nod1) agonists have been shown to boost the inflammatory responses against pathogenic microbes and could thus constitute a new class of broad spectrum antimicrobial agents. To gain additional insight into the structure/activity relationships of Nod1 agonistic compounds, a series of novel, conformationally constrained γ-d-glutamyl- meso-diaminopimelic acid (iE-DAP) analogs have been designed and synthesized. Ramos-Blue cells expressing Nod1 were used to screen and validate our compounds for their Nod1-agonist activity. Their immunomodulatory properties were subsequently determined in vitro, by evaluating their capacity to induce pro-inflammatory cytokine and chemokine production from human peripheral blood mononuclear cells (PBMC), by themselves and in synergy with lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand. The synthesized iE-DAP analogs were shown to possess immuno-enhancing properties as a result of their potent and specific Nod1-agonistic effect. The activity of the compound exhibiting the greatest capacity to induce pro-inflammatory cytokine release from PBMC surpassed that of lauroyl-γ-d-glutamyl-meso-diaminopimelic acid (C12-iE-DAP).
PHIP-label: Parahydrogen-induced polarization in propargylglycine- containing synthetic oligopeptides
Koerner, Marco,Sauer, Grit,Heil, Andreas,Nasu, Daichi,Empting, Martin,Tietze, Daniel,Voigt, Stephan,Weidler, Heiko,Gutmann, Torsten,Avrutina, Olga,Kolmar, Harald,Ratajczyk, Tomasz,Buntkowsky, Gerd
supporting information, p. 7840 - 7841 (2013/09/02)
The unsaturated side chain of l-propargylglycine (Pra) was used to study parahydrogen-induced polarization (PHIP) in synthetic oligopeptides. For the first time PHIP-induced NMR signal enhancement was demonstrated using model peptides bearing various func
