Unleashing the shape of L-DOPA at last

Author(s):  
Miguel Sanz-Novo ◽  
Iker Léon ◽  
Elena Rita Alonso ◽  
Jose Luis Alonso

Herein, we report the first rotational study of neutral L-DOPA, an extensively used supramolecular synthon and an amino acid precursor of the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) using...

Genetics ◽  
1998 ◽  
Vol 150 (1) ◽  
pp. 95-101
Author(s):  
Victor L Boyartchuk ◽  
Jasper Rine

Abstract In eukaryotes small secreted peptides are often proteolytically cleaved from larger precursors. In Saccharomyces cerevisiae multiple proteolytic processing steps are required for production of mature 12-amino-acid a-factor from its 36-amino-acid precursor. This study provides additional genetic data supporting a direct role for Afc1p in cleavage of the carboxyl-terminal tripeptide from the CAAX motif of the prenylated a-factor precursor. In addition, Afc1p had a second role in a-factor processing that was independent of, and in addition to, its role in the carboxyl-terminal processing in vivo. Using ubiquitin-a-factor fusions we confirmed that the pro-region of the a-factor precursor was not required for production of the mature pheromone. However, the pro-region of the a-factor precursor contributed quantitatively to a-factor production.


1987 ◽  
Vol 252 (1) ◽  
pp. E147-E151
Author(s):  
K. D. Bloch ◽  
J. B. Zisfein ◽  
M. N. Margolies ◽  
C. J. Homcy ◽  
J. G. Seidman ◽  
...  

Proatrial natriuretic factor (proANF), the 126-amino acid precursor of ANF, is the major storage form in mammalian atria. In contrast, two ANF peptides containing the 28- and 24-carboxyterminal residues of proANF have been isolated from rat plasma. Whether the cleavage of proANF in vivo to these ANF peptides occurs during or after its release into the circulation has not been determined. The latter possibility was suggested by our previous study where, by using a cultured rat cardiocyte preparation, we demonstrated that proANF is secreted intact into the culture medium. We now report that serum, but not plasma, contains a protease that specifically cleaves the 17-kdalton proANF to a 14-kdalton amino-terminal peptide and the carboxyterminal 3-kdalton circulating forms of ANF. The role of this proANF-cleaving enzyme in the generation of the biologically active ANF peptides remains to be defined. Its isolation and characterization should provide insights into its site of production and whether in vivo it is involved in the processing of circulating proANF.


1999 ◽  
Vol 277 (6) ◽  
pp. R1553-R1561 ◽  
Author(s):  
Craig A. Moore ◽  
Jeffrey D. Kittilson ◽  
Melissa M. Ehrman ◽  
Mark A. Sheridan

Previously, we isolated a 624-bp cDNA encoding for a 115-amino acid preprosomatostatin containing [Tyr7,Gly10]-somatostatin (SS)-14 (now designated PPSS-II′) obtained from the endocrine pancreas (Brockmann bodies) of rainbow trout. In this study we have characterized a second cDNA obtained from trout pancreas that is 600-bp in length and encodes for a 111-amino acid precursor containing [Tyr7,Gly10]-SS-14 (PPSS-II′′). The nucleotide and amino acid identity between the two cDNAs is 82.3 and 80.5%, respectively. Both PPSS-II′ and PPSS-II′′ mRNA were present in esophagus, pyloric ceca, stomach, upper and lower intestine, and pancreas, whereas only SS-II′′ mRNA was present in brain. PPSS-II′′ mRNA was more abundant than PPSS-II′ mRNA in pancreas, whereas PPSS-II′ mRNA was more abundant than PPSS-II′′ mRNA in stomach. Fasting increased pancreatic PPSS-II′′ mRNA levels but had no effect on the levels of PPSS-II′ mRNA. These results indicate the existence of two nonallelic pancreatic SS-II genes that are differentially expressed, both in terms of distribution among tissues and in terms of relative abundance within the tissues.


2012 ◽  
Vol 538 ◽  
pp. A51 ◽  
Author(s):  
H. Møllendal ◽  
L. Margulès ◽  
A. Belloche ◽  
R. A. Motiyenko ◽  
A. Konovalov ◽  
...  

2021 ◽  
Author(s):  
Dung Do

<p></p><p> Development of a rapid synthesis of complex molecules from simple building blocks under a metal-and organocatalyst-free condition is both conceptually and chemically challenging. Here, we developed a hidden catalysis that allow the straightforward assembly of enantiopure aza-tricyclic molecules containing six contiguous stereocenters from <a>aminophenols, α,β-unsaturated aldehydes </a>and α-amino acids. <a>Without using a metal or an organocatalyst, our approach relies on a temporary formation of a spiroimidazolidinone intermediate and its participation in a sequential aza-Michael/Michael reaction as both a substrate and a catalyst</a> under an iminium/enamine catalysis. The formation of the putative iminium intermediate was supported by spectroscopic data and its interruptive reduction derivative was isolated and fully characterized. Whereas a conventional catalyst is always present and does not undergo a permanent chemical change in a classic catalysis, the spiroimidazolidinone intermediate is conceptualized as a sub-catalyst as it is only temporary produced from precursors and catalyzes its own consumption. This unique substrate-catalyst (sub-catalyst) dual role of the spiroimidazolidinone induces a substantial steric discrimination in the transition state and an excellent overall diastereoselectivity (>20:1 dr). It allows the use of an amino acid precursor as the sole chirality genesis and avoids the use of transition metals or organocatalysts. An enantiomer of an aza-tricyclic imidazolidinone can be prepared from a commercially available amino acid precursor. The aqueous-based reaction is practical and scalable for multi-gram synthesis. The success of implementing this sub-catalysis concept in the synthesis will pave the way for many efficient chiral catalyst-free preparations of chiral complex molecules.<br></p><br><p></p>


Cephalalgia ◽  
1994 ◽  
Vol 14 (5) ◽  
pp. 352-356 ◽  
Author(s):  
G D'Andrea ◽  
AR Cananzi ◽  
F Perini ◽  
M Alecci ◽  
F Zamberlan ◽  
...  

We studied whole blood platelet aggregation induced by collagen, platelet activating factor (PAF) and measured basal platelet L-arginine (L-arg) levels, as an indirect index of the nitric oxide (NO) pathway in migraine. Migraine, both with and without aura groups, showed a reduced aggregation to collagen, but not to PAF, compared with control subjects. Platelet L-arg levels were significantly increased in migraine with aura sufferers, whereas the plasma levels were in the same range in migraineurs and controls. Platelet hyperesponsiveness to collagen stimulation in migraine may be linked to an increased availability of the amino acid precursor and an abnormal NO synthesis.


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