Chemo-selective cross reaction of two enals via carbene-catalyzed dual activation

Xiaolin Peng; Jun Xu; Tingting Li; Yonggui Robin Chi; Zhichao Jin

doi:10.1039/d0sc03297b

Chemo-selective cross reaction of two enals via carbene-catalyzed dual activation

Chemical Science ◽

10.1039/d0sc03297b ◽

2020 ◽

Vol 11 (46) ◽

pp. 12533-12539

Author(s):

Xiaolin Peng ◽

Jun Xu ◽

Tingting Li ◽

Yonggui Robin Chi ◽

Zhichao Jin

Keyword(s):

Cross Reaction ◽

Dual Activation ◽

Activation Pathways ◽

Covalent Activation

An NHC-catalyzed dual activation of two different enals is disclosed with both covalent and non-covalent activation pathways involved.

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The Impact of the HydroxyMethylCytosine epigenetic signature on DNA structure and function

PLoS Computational Biology ◽

10.1371/journal.pcbi.1009547 ◽

2021 ◽

Vol 17 (11) ◽

pp. e1009547

Author(s):

Federica Battistini ◽

Pablo D. Dans ◽

Montserrat Terrazas ◽

Chiara L. Castellazzi ◽

Guillem Portella ◽

...

Keyword(s):

Physical Properties ◽

Cytosine Methylation ◽

Dna Binding Domains ◽

Binding Domains ◽

Lower Ability ◽

Dual Activation ◽

Activation Pathways ◽

And Function ◽

The Impact ◽

Rule Out

We present a comprehensive, experimental and theoretical study of the impact of 5-hydroxymethylation of DNA cytosine. Using molecular dynamics, biophysical experiments and NMR spectroscopy, we found that Ten-Eleven translocation (TET) dioxygenases generate an epigenetic variant with structural and physical properties similar to those of 5-methylcytosine. Experiments and simulations demonstrate that 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) generally lead to stiffer DNA than normal cytosine, with poorer circularization efficiencies and lower ability to form nucleosomes. In particular, we can rule out the hypothesis that hydroxymethylation reverts to unmodified cytosine physical properties, as hmC is even more rigid than mC. Thus, we do not expect dramatic changes in the chromatin structure induced by differences in physical properties between d(mCpG) and d(hmCpG). Conversely, our simulations suggest that methylated-DNA binding domains (MBDs), associated with repression activities, are sensitive to the substitution d(mCpG) ➔ d(hmCpG), while MBD3 which has a dual activation/repression activity is not sensitive to the d(mCpG) d(hmCpG) change. Overall, while gene activity changes due to cytosine methylation are the result of the combination of stiffness-related chromatin reorganization and MBD binding, those associated to 5-hydroxylation of methylcytosine could be explained by a change in the balance of repression/activation pathways related to differential MBD binding.

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The Impact of The Hydroxymethyl-Cytosine Epigenetic Signature on DNA Structure And Function

10.1101/2020.09.17.285452 ◽

2020 ◽

Author(s):

Federica Battistini ◽

Pablo D. Dans ◽

Montserrat Terrazas ◽

Chiara L. Castellazzi ◽

Guillem Portella ◽

...

Keyword(s):

Physical Properties ◽

Cytosine Methylation ◽

Dna Binding Domains ◽

Binding Domains ◽

Hydroxymethyl Cytosine ◽

Lower Ability ◽

Dual Activation ◽

Activation Pathways ◽

And Function ◽

The Impact

ABSTRACTWe present a comprehensive, experimental and theoretical study of the impact of 5-hydroxymethylation of DNA cytosine. Using molecular dynamics, biophysical experiments and NMR spectroscopy, we found that Ten-Eleven translocation (TET) dioxygenases generate an epigenetic variant with structural and physical properties not too different to those of 5-methylcytosine. Experiments and simulations demonstrate that 5-methyl-cytosine (mC) and 5-hydroxymethyl-cytosine (hmC) generally lead to more rigid duplexes with poorer circularization efficiencies and lower ability to form nucleosomes. In particular, we can rule out the hypothesis that hydroxymethylation reverts to unmodified cytosine physical properties, as hmC is even more rigid than mC. Thus, we do not expect dramatic changes in the chromatin structure induced by differences in physical properties between d(mCpG) and d(hmCpG). On the contrary, our simulations suggest that methylated-DNA binding domains (MBD), associated with repression activities, are very sensitive to the substitution d(mCpG)→ d(hmCpG), while MBD3 which has a dual activation/repression activity is not sensitive to the d(mCpG) → d(hmCpG) change. Overall, while changes in gene activity due to cytosine methylation are the result of the combination of stiffness-related chromatin reorganization and MBD binding, those associated to 5-hydroxylation of methylcytosine could be explained by a change in the balance of repression/activation pathways related to differential MBD binding.

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Pharmacodynamics of [D-Ser (t-Bu), Des-Gly]GnRH ethylamide (Buserelin®) in 6 normal volunteers.

Acta Endocrinologica ◽

10.1530/acta.0.1150235 ◽

1987 ◽

Vol 115 (2) ◽

pp. 235-242 ◽

Cited By ~ 3

Author(s):

Y. Reznik ◽

B. P. Winiger ◽

M. L. Aubert ◽

P. C. Sizonenko

Keyword(s):

Urinary Excretion ◽

Precocious Puberty ◽

Plasma Levels ◽

Intranasal Administration ◽

Cross Reaction ◽

Disappearance Rate ◽

Gnrh Analog ◽

Male Adolescents ◽

Normal Volunteers ◽

The Mean

Abstract. The disappearance rate of [D-Ser(t-bu)6,des-Gly10]GnRH ethylamide (Buserelin®, HOE 766) was studied in plasma and urine after intranasal (300 μg) or sc (10 μg/kg) administration. A radioimmunoassay for HOE 766 was developed using 125I[D-Trp6,Des-Gly10]GnRH ethylamide as tracer and an antiserum raised against HOE 766. Cross-reaction with native GnRH was only 1.7%. Sensitivity was 1 pg/tube. In 6 male adolescents, the mean plasma HOE 766 concentration (± sem) was 0.46 ± 0.08, 0.50 ± 0.10, 0.28 ± 0.04, 0.24 ± 0.04, 0.13 ± 0.03, and 0.08 ± 0.02 μg/l 30, 60, 90, 120 and 180 min after the intranasal administration, respectively. Concomitant urinary excretion of HOE 766-like material was 9.43 ± 1.96 μg/4 h. There was a good correlation between integrated plasma levels and urinary excretion (r = 0.92). In the same 6 volunteers, the plasma HOE 766 levels were 21.2 ± 3.0, 25.9 ± 0.8, 21.2 ± 0.9, 17.1 ± 0.7, 12.8 ± 1.1, 8.9 ± 0.4, and 5.9 ± 0.8 μg/l 20, 40, 60, 90, 120, 180 and 240 min after sc injection, respectively. The mean urinary excretion was 543 ± 61 μg/4 h. In two girls with precocious puberty treated during 12 to 15 months with intranasal administration of HOE 766, urinary excretion of HOE 766-like material was shown to correlate well with the degree of inhibition of plasma 17β-E2and of plasma LH and FSH responses to a GnRH challenge. Thus, monitoring of HOE 766 in urine appears to be helpful for evaluating of intranasal therapy with a GnRH analog in precocious puberty.

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