scholarly journals A modular and divergent approach to spirocyclic pyrrolidines

2020 ◽  
Vol 11 (38) ◽  
pp. 10354-10360 ◽  
Author(s):  
Benjamin D. A. Shennan ◽  
Peter W. Smith ◽  
Yusuke Ogura ◽  
Darren J. Dixon
Keyword(s):  

A three-step, modular and divergent sequence accessing challenging spirocyclic pyrrolidines has been developed, featuring a novel reductive spirocyclization cascade.

Genetics ◽  
1997 ◽  
Vol 147 (1) ◽  
pp. 297-304
Author(s):  
Heidi Scrable ◽  
Peter J Stambrook

Abstract We have introduced sequences encoding the lac repressor of Escherichia coli into the genome of the mouse. One sequence was derived from the bacterial lac operon and the other was created by reencoding the amino acid sequence of lacI with mammalian codons. Both versions are driven by an identical promoter fragment derived from the human β-actin locus and were microinjected into genetically identical pronuclear stage embryos. All transgenes utilizing the bacterial coding sequence were transcriptionally silent in all somatic tissues tested. The sequence re-encoded with mammalian codons was transcriptionally active at all transgene loci and expressed ubiquitously. Using methylation-sensitive enzymes, we have determined the methylation status of lac repressor transgenes encoded by either the bacterial or mammalian sequence. The highly divergent bacterial sequence was hypermethylated at all transgene loci, while the mammalian sequence was only hypermethylated at a high copy number locus. This may reflect a normal process that protects the genome from acquiring new material that has an abnormally divergent sequence or structure.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2160
Author(s):  
Guido Gambacorta ◽  
David C. Apperley ◽  
Ian R. Baxendale

The hydroxy-pyrazole and 3-hydroxy-oxindole motifs have been utilised in several pharma and agrochemical leads but are distinctly underrepresented in the scientific literature due to the limited routes of preparation. We have developed a one-pot procedure for their synthesis starting from simple isatins. The method employs cheap and easy-to-handle building blocks and allows easy isolation.


2000 ◽  
Vol 182 (23) ◽  
pp. 6798-6805 ◽  
Author(s):  
Sergio R. Filipe ◽  
Elena Severina ◽  
Alexander Tomasz

ABSTRACT The presence and sequence variation of the murM gene were studied in a large collection (814 strains) of genetically diverseStreptococcus pneumoniae isolates, which included 27 different serogroups and both penicillin-resistant (423 isolates, 67 pulsed-field gel electrophoretic [PFGE] types) and intermediately penicillin-resistant (165 isolates, 66 PFGE types) and penicillin-susceptible (226 isolates, 135 PFGE types) strains. Diversity of the murM sequences was tested by hybridization with mainly two kinds of probes: one derived from the amplification of the nucleotide sequence between nucleotides 201 and 624 in the penicillin-susceptible laboratory strain R36A (murMA probe) and a second probe that amplified the comparable, highly divergent sequence in the penicillin-resistant strain Pen6 (murMBprobe). The great majority of the strains (761 of 814), including both penicillin-susceptible and penicillin-resistant isolates, reacted exclusively with the murMA probe. A smaller group of penicillin-resistant strains (48 of 814 isolates) reacted only with themurMB DNA probe, and an additional 5 isolates reacted with both probes. High-pressure liquid chromatography analysis of the peptidoglycan of strains hybridizing with murMB showed that they invariably contained an increased proportion of branched peptides. Complete sequencing of murM from a group of penicillin-resistant isolates allowed the identification of a number of different murMB alleles that differed in the length and exact position of the divergent (Pen6 type) sequences within the particular murM. The close similarity of these divergent sequences in the various murM alleles suggests a possible common heterologous origin.


1992 ◽  
Vol 12 (3) ◽  
pp. 1107-1116 ◽  
Author(s):  
P Qasba ◽  
E Lin ◽  
M D Zhou ◽  
A Kumar ◽  
M A Siddiqui

The cardiac myosin light chain-2 (MLC-2) gene promoter contains several positive and negative cis-acting sequences that are involved in the regulation of its expression. We describe here the properties of two activator sequences, elements A and P, and their DNA-binding factors (ABFs). Element A (CCAAAAGTGG), located at -61, has homology with the evolutionarily conserved sequence CC(A/T)6GG, present in the genes of many contractile proteins. Element P (TAACCTTGAAAGC), located 114 bp upstream of element A, is conserved in both chicken and rat cardiac MLC-2 gene promoters. Deletion mutagenesis demonstrated that these two elements are involved in the positive regulation of MLC-2 gene transcription. At least two sequence-specific element A-binding proteins, ABF-1 and ABF-2, were identified by gel shift analysis of the fractionated cardiac nuclear proteins. ABF-1 binds to element A with strict dependence on the internal element A sequence AAAAGT. In contrast, ABF-2 exhibits a relaxed sequence requirement, as it recognizes the consensus CArG and CCAAT box sequences as well. ABF-2 also recognizes the distal element P despite the fact that the sequences of elements A and P are divergent. DNase I footprinting, methylation interference, and gel shift analyses demonstrated unequivocally that the element A-DNA affinity-purified protein ABF-2 binds to element P with sequence specificity. Since both elements A and P play a positive regulatory role in MLC-2 gene transcription and bind to a single protein (ABF-2), it would appear that ABF-2 is a key transcription factor with the ability to recognize divergent sequence elements involved in a common regulatory pathway during myogenesis.


2019 ◽  
Vol 75 (1) ◽  
Author(s):  
André Pierro de Camargo
Keyword(s):  

FEBS Letters ◽  
1995 ◽  
Vol 374 (2) ◽  
pp. 246-248 ◽  
Author(s):  
Stephen F. Haydock ◽  
Jesús F. Aparicio ◽  
István Molnár ◽  
Torsten Schwecke ◽  
Lake Ee Khaw ◽  
...  

Filomat ◽  
2013 ◽  
Vol 27 (4) ◽  
pp. 625-627 ◽  
Author(s):  
Richard Patterson

In 1946 P. Erdos and P. C Rosenbloom presented the following theorem that arose out of discussions they had with R. P. Agnew. Let {xn} be a bounded divergent sequence. Suppose that {xn} is summable by every regular Toeplitz method which sums {xn}. Then {yn} is of the form {cxn + an} where {an} is convergent. The goals of the paper includes the presentation of a multidimensional analog of Erdos and Rosenbloom results in [1].


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