Autocatalysis and organocatalysis with synthetic structures.
Ontology highlight
ABSTRACT:
SUBMITTER: Kamioka S
PROVIDER: S-EPMC2818938 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The cyclization reaction of an epoxyalcohol is catalyzed by a synthetic cavitand receptor with an inwardly directed carboxylic acid function. The receptor features a hydrophobic pocket in which the substrate is bound and positioned to react in a regioselective manner. The nature of this substrate-catalyst complex and its dynamic properties were investigated by NMR methods and with the aid of a model compound lacking the epoxide function. The kinetic parameters of the cyclization reaction were also studied. A catalytic cycle is proposed and diverse inhibition mechanisms are identified that parallel those encounterd in enzymology.
| S-EPMC2720318 | biostudies-literature
Project description:Ortholithiation of 3-fluorophenyl-N,N-diisopropyl carbamate by lithium diisopropylamide (LDA) in THF at -78 degrees C affords unusual rate behavior including linear decays of the carbamate, delayed formation of LDA-aryllithium mixed dimers, and evidence of autocatalysis. A mechanistic model in conjunction with numeric integration methods accounts for the time-dependent changes in concentration. The two critical rate-limiting steps in the model entail (1) an LDA dimer-based metalation of arylcarbamate, and (2) a rate-limiting condensation of the resulting aryllithium with the LDA dimer to form two isomeric LDA-ArLi mixed dimers. One isomer elicits a highly efficient (post-rate-limiting) metalation of aryl carbamate, in turn, regenerating aryllithium. The prevalence and implications of such autocatalysis are discussed.
| S-EPMC2643095 | biostudies-literature
Project description:We developed an efficient method to generate porcine blastocyst-like structures (termed blastoids) from ESCs.
2024-06-30 | GSE242553 | GEO
Project description:The photoprotein aequorin emits light by an intramolecular reaction in the presence of a trace amount of Ca(2+). Semi-synthetic aequorins, produced by replacing the coelenterazine moiety in aequorin with the analogues of coelenterazine, show widely different sensitivities to Ca(2+). To understand the structural basis of the Ca(2+)-sensitivity, we determined the crystal structures of four semi-synthetic aequorins (cp-, i-, br- and n-aequorins) at resolutions of 1.6-1.8 A. In general, the protein structures of these semi-synthetic aequorins are almost identical to native aequorin. Of the four EF-hand domains in the molecule, EF-hand II does not bind Ca(2+), and the loop of EF-hand IV is clearly deformed. It is most likely that the binding of Ca(2+) with EF-hands I and III triggers luminescence. Although little difference was found in the overall structures of aequorins investigated, some significant differences were found in the interactions between the substituents of coelenterazine moiety and the amino acid residues in the binding pocket. The coelenterazine moieties in i-, br-, and n-aequorins have bulky 2-substitutions, which can interfere with the conformational changes of protein structure that follow the binding of Ca(2+) to aequorin. In cp-aequorin, the cyclopentylmethyl group that substitutes for the original 8-benzyl group does not interact hydrophobically with the protein part, giving the coelenterazine moiety more conformational freedom to promote the light-emitting reaction. The differences of various semi-synthetic aequorins in Ca(2+)-sensitivity and reaction rate are explained by the capability of the involved groups and structures to undergo conformational changes in response to the Ca(2+)-binding.
| S-EPMC2253417 | biostudies-literature
Project description:Cross-conjugated trienamines are introduced as a new concept in asymmetric organocatalysis. These intermediates are applied in highly enantioselective Diels-Alder and addition reactions, providing functionalized bicyclo[2.2.2]octane compounds and γ'-addition products, respectively. The nature of the transformations and the intermediates involved are investigated by computational calculations and NMR analysis.
| S-EPMC3557926 | biostudies-literature
Project description:Organocatalysis is an emerging field, in which small metal-free organic structures catalyze a diversity of reactions with a remarkable stereoselectivity. The ability to selectively switch on such pathways upon demand has proven to be a valuable tool in biological systems. Light as a trigger provides the ultimate spatial and temporal control of activation. However, there have been limited examples of phototriggered catalytic systems. Herein, we describe the synthesis and application of a caged proline system that can initiate organocatalysis upon irradiation. The caged proline was generated using the highly efficient 4-carboxy-5,7-dinitroindolinyl (CDNI) photocleavable protecting group in a four-step synthesis. Advantages of this system include water solubility, biocompatibility, high quantum yield for catalyst release, and responsiveness to two-photon excitation. We showed the light-triggered catalysis of a crossed aldol reaction, a Mannich reaction, and a self-aldol condensation reaction. We also demonstrated light-initiated catalysis, leading to the formation of a biocide in situ, which resulted in the growth inhibition of E. coli, with as little as 3 min of irradiation. This technique can be broadly applied to other systems, by which the formation of active forms of drugs can be catalytically assembled remotely via two-photon irradiation.
| S-EPMC6510250 | biostudies-literature
Project description:The L-shape form of tRNA is maintained by tertiary interactions occurring in the core. Base changes in this domain can cause structural defects and impair tRNA activity. Here, we report on a method to safely engineer structural variations in this domain utilizing the noncanonical scaffold of tRNAPyl. First, we constructed a naïve hybrid between archaeal tRNAPyl and tRNATyr, which consisted of the acceptor and T stems of tRNATyr and the other parts of tRNAPyl. This hybrid tRNA efficiently translated the UAG codon to 3-iodotyrosine in Escherichia coli cells, when paired with a variant of the archaeal tyrosyl-tRNA synthetase. The amber suppression efficiency was slightly lower than that of the "bench-mark" archaeal tRNATyr suppressor assuming the canonical structure. After a series of modifications to this hybrid tRNA, we obtained two artificial types of tRNATyr: ZtRNA had an augmented D (auD) helix in a noncanonical form and the D and T loops bound by the standard tertiary base pairs, and YtRNA had a canonical auD helix and non-standard interloop interactions. It was then suggested that the ZtRNA scaffold could also support the glycylation and glutaminylation of tRNA. The synthetic diversity of tRNA would help create new tRNA?aminoacyl-tRNA synthetase pairs for reprogramming the genetic code.
| S-EPMC6337575 | biostudies-literature
Project description:To investigate the mechanisms underlying the rearrangement patterns,we compared the rearrangement map with local chromatin structures and the three-dimensional genome architecture via assay for transposase-accessible chromatin using sequencing (ATAC-seq) and genome-wide chromosome conformation capture (Hi-C), respectively
2022-06-10 | GSE168182 | GEO
Project description:Helical secondary and tertiary motifs are commonly observed as binding epitopes in natural and engineered protein scaffolds. While several strategies have been described to constrain α-helices or reproduce their binding attributes in synthetic mimics, general strategies to mimic tertiary helical motifs remain in their infancy. We recently described a synthetic strategy to develop helical dimers ( J. Am. Chem. Soc. 2015, 137, 11618-11621). We found that replacement of an interhelical salt bridge with a covalent bond can stabilize antiparallel motifs in short sequences. Here we show that the approach can be generalized to obtain antiparallel and parallel dimers as well as trimer motifs. Helical stabilization requires judiciously designed cross-linkers as well as optimal interhelical hydrophobic packing. We anticipate that these mimics would afford new classes of modulators of biological function.
| S-EPMC7768809 | biostudies-literature
Project description:The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. MultiBac has allowed the structure and function of many molecular machines to be elucidated, including previously inaccessible high-value drug targets. More recently, MultiBac developments have shifted to customized baculoviral genomes that are tailored for a range of applications, including synthesizing artificial proteins by genetic code expansion. We review some of these developments, including the ongoing rewiring of the MultiBac system for mammalian applications, notably CRISPR/Cas9-mediated gene editing.
| S-EPMC5661938 | biostudies-literature