scholarly journals Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

2014 ◽  
Vol 10 ◽  
pp. 2566-2572 ◽  
Author(s):  
Vicky Gheerardijn ◽  
Jos Van den Begin ◽  
Annemieke Madder
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Nucleic Acid ◽  
Functional Groups ◽  
Functional Group ◽  
Binding Properties ◽  
Dna And Rna ◽  
Straightforward Method ◽  
Nucleic Acid Structures ◽  
Proof Of Principle

Functionalized oligonucleotides have recently gained increased attention for incorporation in modified nucleic acid structures both for the design of aptamers with enhanced binding properties as well as the construction of catalytic DNA and RNA. As a shortcut alternative to the incorporation of multiple modified residues, each bearing one extra functional group, we present here a straightforward method for direct linking of functionalized amino acids to the nucleoside base, thus equipping the nucleoside with two extra functionalities at once. As a proof of principle, we have introduced three amino acids with functional groups frequently used as key-intermediates in DNA- and RNAzymes via an efficient and straightforward domino carboxamidation reaction.

scholarly journals Saccharomyces cerevisiae SSB1 protein and its relationship to nucleolar RNA-binding proteins

1987 ◽  
Vol 7 (8) ◽  
pp. 2947-2955
Author(s):  
A Y Jong ◽  
M W Clark ◽  
M Gilbert ◽  
A Oehm ◽  
J L Campbell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Nucleic Acid ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nucleic Acid Binding ◽  
Dna And Rna ◽  
C Terminus

To better define the function of Saccharomyces cerevisiae SSB1, an abundant single-stranded nucleic acid-binding protein, we determined the nucleotide sequence of the SSB1 gene and compared it with those of other proteins of known function. The amino acid sequence contains 293 amino acid residues and has an Mr of 32,853. There are several stretches of sequence characteristic of other eucaryotic single-stranded nucleic acid-binding proteins. At the amino terminus, residues 39 to 54 are highly homologous to a peptide in calf thymus UP1 and UP2 and a human heterogeneous nuclear ribonucleoprotein. Residues 125 to 162 constitute a fivefold tandem repeat of the sequence RGGFRG, the composition of which suggests a nucleic acid-binding site. Near the C terminus, residues 233 to 245 are homologous to several RNA-binding proteins. Of 18 C-terminal residues, 10 are acidic, a characteristic of the procaryotic single-stranded DNA-binding proteins and eucaryotic DNA- and RNA-binding proteins. In addition, examination of the subcellular distribution of SSB1 by immunofluorescence microscopy indicated that SSB1 is a nuclear protein, predominantly located in the nucleolus. Sequence homologies and the nucleolar localization make it likely that SSB1 functions in RNA metabolism in vivo, although an additional role in DNA metabolism cannot be excluded.

scholarly journals Natural Products Containing ‘Rare’ Organophosphorus Functional Groups

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 866 ◽  
Author(s):  
Janusz Petkowski ◽  
William Bains ◽  
Sara Seager
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Functional Groups ◽  
Functional Group ◽  
Organophosphorus Compounds ◽  
Living Cells ◽  
Unusual Amino Acids ◽  
Biological Source ◽  
Technological Limitations

Phosphorous-containing molecules are essential constituents of all living cells. While the phosphate functional group is very common in small molecule natural products, nucleic acids, and as chemical modification in protein and peptides, phosphorous can form P–N (phosphoramidate), P–S (phosphorothioate), and P–C (e.g., phosphonate and phosphinate) linkages. While rare, these moieties play critical roles in many processes and in all forms of life. In this review we thoroughly categorize P–N, P–S, and P–C natural organophosphorus compounds. Information on biological source, biological activity, and biosynthesis is included, if known. This review also summarizes the role of phosphorylation on unusual amino acids in proteins (N- and S-phosphorylation) and reviews the natural phosphorothioate (P–S) and phosphoramidate (P–N) modifications of DNA and nucleotides with an emphasis on their role in the metabolism of the cell. We challenge the commonly held notion that nonphosphate organophosphorus functional groups are an oddity of biochemistry, with no central role in the metabolism of the cell. We postulate that the extent of utilization of some phosphorus groups by life, especially those containing P–N bonds, is likely severely underestimated and has been largely overlooked, mainly due to the technological limitations in their detection and analysis.

scholarly journals Primordial emergence of a nucleic acid-binding protein via phase separation and statistical ornithine-to-arginine conversion

2020 ◽  
Vol 117 (27) ◽  
pp. 15731-15739 ◽  
Author(s):  
Liam M. Longo ◽  
Dragana Despotović ◽  
Orit Weil-Ktorza ◽  
Matthew J. Walker ◽  
Jagoda Jabłońska ◽  
...  
Keyword(s):  
Amino Acids ◽  
Phase Separation ◽  
Amino Acid ◽  
Nucleic Acid ◽  
Binding Protein ◽  
Basic Amino Acid ◽  
Nucleic Acid Binding ◽  
Evolutionary Trajectory ◽  
Nucleic Acid Binding Protein ◽  
Acid Binding Protein

De novo emergence demands a transition from disordered polypeptides into structured proteins with well-defined functions. However, can polypeptides confer functions of evolutionary relevance, and how might such polypeptides evolve into modern proteins? The earliest proteins present an even greater challenge, as they were likely based on abiotic, spontaneously synthesized amino acids. Here we asked whether a primordial function, such as nucleic acid binding, could emerge with ornithine, a basic amino acid that forms abiotically yet is absent in modern-day proteins. We combined ancestral sequence reconstruction and empiric deconstruction to unravel a gradual evolutionary trajectory leading from a polypeptide to a ubiquitous nucleic acid-binding protein. Intermediates along this trajectory comprise sequence-duplicated functional proteins built from 10 amino acid types, with ornithine as the only basic amino acid. Ornithine side chains were further modified into arginine by an abiotic chemical reaction, improving both structure and function. Along this trajectory, function evolved from phase separation with RNA (coacervates) to avid and specific double-stranded DNA binding. Our results suggest that phase-separating polypeptides may have been an evolutionary resource for the emergence of early proteins, and that ornithine, together with its postsynthesis modification to arginine, could have been the earliest basic amino acids.

Effect of hypophysectomy on amino acid, thymidine, and orotic acid incorporation into the mucosa of the small bowel

1970 ◽  
Vol 48 (7) ◽  
pp. 828-830 ◽  
Author(s):  
Reuven Levitan ◽  
Eli Havivi
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Small Bowel ◽  
Intestinal Mucosa ◽  
Orotic Acid ◽  
Tritiated Thymidine ◽  
Dna And Rna ◽  
Acid Incorporation

After hypophysectomy, the incorporation of tritiated thymidine and orotic acid into DNA and RNA, respectively, decreased in the intestinal mucosa. Hypophysectomy lowered the incorporation of amino acids into protein in vitro, yet the proportion of polysomes remained unaltered. After hypophysectomy, the polysomes were impaired in their ability to incorporate amino acids in vitro.

DNA and RNA binding properties of an arginine-based ‘Extended Chiral Box’ Peptide Nucleic Acid

2011 ◽  
Vol 52 (2) ◽  
pp. 300-304 ◽  
Author(s):  
Alessandro Calabretta ◽  
Tullia Tedeschi ◽  
Roberto Corradini ◽  
Rosangela Marchelli ◽  
Stefano Sforza
Keyword(s):  
Nucleic Acid ◽  
Peptide Nucleic Acid ◽  
Rna Binding ◽  
Binding Properties ◽  
Dna And Rna ◽  
Dna And Rna Binding

scholarly journals Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

2017 ◽  
Vol 13 ◽  
pp. 2428-2441 ◽  
Author(s):  
Matthias Wünsch ◽  
David Schröder ◽  
Tanja Fröhr ◽  
Lisa Teichmann ◽  
Sebastian Hedwig ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Asymmetric Synthesis ◽  
Functional Groups ◽  
Amide Bond ◽  
Side Chain ◽  
Side Reactions ◽  
Mild Conditions ◽  
Protective Groups ◽  
Polar Functional Groups

The amide moiety of peptides can be replaced for example by a triazole moiety, which is considered to be bioisosteric. Therefore, the carbonyl moiety of an amino acid has to be replaced by an alkyne in order to provide a precursor of such peptidomimetics. As most amino acids have a chiral center at Cα, such amide bond surrogates need a chiral moiety. Here the asymmetric synthesis of a set of 24N-sulfinyl propargylamines is presented. The condensation of various aldehydes with Ellman’s chiral sulfinamide provides chiralN-sulfinylimines, which were reacted with (trimethylsilyl)ethynyllithium to afford diastereomerically pureN-sulfinyl propargylamines. Diverse functional groups present in the propargylic position resemble the side chain present at the Cαof amino acids. Whereas propargylamines with (cyclo)alkyl substituents can be prepared in a direct manner, residues with polar functional groups require suitable protective groups. The presence of particular functional groups in the side chain in some cases leads to remarkable side reactions of the alkyne moiety. Thus, electron-withdrawing substituents in the Cα-position facilitate a base induced rearrangement to α,β-unsaturated imines, while azide-substituted propargylamines form triazoles under surprisingly mild conditions. A panel of propargylamines bearing fluoro or chloro substituents, polar functional groups, or basic and acidic functional groups is accessible for the use as precursors of peptidomimetics.

scholarly journals High-yield fabrication of DNA and RNA constructs for single molecule force and torque spectroscopy experiments

2019 ◽  
Vol 47 (22) ◽  
pp. e144-e144 ◽  
Author(s):  
Flávia S Papini ◽  
Mona Seifert ◽  
David Dulin
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Single Molecule ◽  
Magnetic Tweezers ◽  
High Yield ◽  
High Quality ◽  
Single Molecule Biophysics ◽  
Dna And Rna ◽  
Rna Hairpins ◽  
Nucleic Acid Structures

Abstract Single molecule biophysics experiments have enabled the observation of biomolecules with a great deal of precision in space and time, e.g. nucleic acids mechanical properties and protein–nucleic acids interactions using force and torque spectroscopy techniques. The success of these experiments strongly depends on the capacity of the researcher to design and fabricate complex nucleic acid structures, as the outcome and the yield of the experiment also strongly depend on the high quality and purity of the final construct. Though the molecular biology techniques involved are well known, the fabrication of nucleic acid constructs for single molecule experiments still remains a difficult task. Here, we present new protocols to generate high quality coilable double-stranded DNA and RNA, as well as DNA and RNA hairpins with ∼500–1000 bp long stems. Importantly, we present a new approach based on single-stranded DNA (ssDNA) annealing and we use magnetic tweezers to show that this approach simplifies the fabrication of complex DNA constructs, such as hairpins, and converts more efficiently the input DNA into construct than the standard PCR-digestion-ligation approach. The protocols we describe here enable the design of a large range of nucleic acid construct for single molecule biophysics experiments.

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