Development of 2-aminoisobutyric acid (Aib)-rich cell-penetrating foldamers for efficient siRNA delivery

2019 ◽  
Vol 55 (54) ◽  
pp. 7792-7795 ◽  
Author(s):  
Takashi Misawa ◽  
Nobumichi Ohoka ◽  
Makoto Oba ◽  
Hiroko Yamashita ◽  
Masakazu Tanaka ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Sirna Delivery ◽  
Aminoisobutyric Acid ◽  
Cell Penetrating ◽  
The Common

We have designed and synthesized a set of cell-penetrating foldamers (CPFs), Blocks 1–8, composed of the common amino acids Leu, Arg, and Gly, as well as the helicogenic amino acid 2-aminoisobutyric acid.

scholarly journals WRAP-based nanoparticles for siRNA delivery: a SAR study and a comparison with lipid-based transfection reagents

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Karidia Konate ◽  
Emilie Josse ◽  
Milana Tasic ◽  
Karima Redjatti ◽  
Gudrun Aldrian ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gene Silencing ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Sirna Delivery ◽  
Cell Penetrating Peptides ◽  
Sirna Transfection ◽  
Arginine Residues ◽  
Sar Study

AbstractRecently, we designed novel amphipathic cell-penetrating peptides, called WRAP, able to transfer efficiently siRNA molecules into cells. In order to gain more information about the relationship between amino acid composition, nanoparticle formation and cellular internalization of these peptides composed of only three amino acids (leucine, arginine and tryptophan), we performed a structure–activity relationship (SAR) study. First, we compared our WRAP1 and WRAP5 peptides with the C6M1 peptide also composed of the same three amino acids and showing similar behaviors in siRNA transfection. Afterwards, to further define the main determinants in the WRAP activity, we synthesized 13 new WRAP analogues harboring different modifications like the number and location of leucine and arginine residues, the relative location of tryptophan residues, as well as the role of the α-helix formation upon proline insertions within the native WRAP sequence. After having compared the ability of these peptides to form peptide-based nanoparticles (PBNs) using different biophysical methods and to induce a targeted gene silencing in cells, we established the main sequential requirements of the amino acid composition of the WRAP peptide. In addition, upon measuring the WRAP-based siRNA transfection ability into cells compared to several non-peptide transfection agents available on the markets, we confirmed that WRAP peptides induced an equivalent level of targeted gene silencing but in most of the cases with lower cell toxicity as clearly shown in clonogenic assays.

scholarly journals A Practical Approach to the Investigation of Amino Acid Disorders

1988 ◽  
Vol 25 (2) ◽  
pp. 129-141 ◽  
Author(s):  
M A Edwards ◽  
S Grant ◽  
A Green
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Analysis ◽  
Practical Approach ◽  
The Common ◽  
Common Problems

We have, in this paper, highlighted some of the common problems in amino acid analysis in our experience and listed the possible causes for increases in specific amino acids in urine—together with guidance on appropriate follow-up investigations.

Renal reabsorption of amino acids

1962 ◽  
Vol 203 (5) ◽  
pp. 891-896 ◽  
Author(s):  
Marian Ruszkowski ◽  
Cizesław Arasimowicz ◽  
Jan Knapowski ◽  
Jan Steffen ◽  
Krystyna Weiss
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Transport Mechanism ◽  
Flow Analysis ◽  
Proximal Segment ◽  
Renal Tubules ◽  
Basic Amino Acids ◽  
Tubular Transport ◽  
The Common ◽  
Stop Flow

Using the method of stop flow analysis an attempt was made to localize the process of amino acid reabsorption in the nephron of the dog. Special attention was given to the group of basic amino acids and cystine believed to share a common tubular transport mechanism. The evidence obtained in this study points clearly to the proximal segment as the site of intensive reabsorption of all amino acids investigated. During the infusion of arginine, lysine or ornithine, an increased excretion of two remaining basic amino acids plus cystine was observed, as a rule. Successful attempts were made to infuse cystine intravenously. The results of these experiments did provide the missing link for the hypothesis derived by Dent and Rose ( Quart. J. Med. 20: 205, 1951) concerning the common transport mechanism of arginine, ornithine, lysine, and cystine in the renal tubules. The functional cystinuria, which can be induced by saturating the common reabsorptive pathway with each of the above-mentioned amino acids, is fully reversible.

scholarly journals Amino acid uptake in isolated chick embryo heart cells. Effect of insulin

1969 ◽  
Vol 114 (1) ◽  
pp. 97-105 ◽  
Author(s):  
G. G. Guidotti ◽  
Britta Lüneburg ◽  
A. F. Borghetti
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Chick Embryo ◽  
Isolated Heart ◽  
Cardiac Cells ◽  
Cell Permeability ◽  
Heart Cells ◽  
Acid Uptake ◽  
Aminoisobutyric Acid ◽  
Isolated Heart Cells

1. The preparation of cell suspensions by treatment of chick embryo hearts with collagenase at various stages of development is described. 2. Measurements of oxygen consumption, incorporation of labelled leucine into protein and accumulation of labelled α-aminoisobutyric acid against a concentration gradient indicated a long-lasting viability of the isolated heart cells in vitro; a satisfactory preservation of subcellular structures, including plasma membrane, was assessed by electron-microscopic examination. 3. The rate of α-aminoisobutyric acid accumulation by cardiac cells isolated from hearts at different stages of embryological development decreased with aging; insulin stimulated the intracellular accumulation of this amino acid analogue. 4. Insulin increased the uptake by isolated heart cells of several 14C-labelled naturally occurring amino acids; however, the fraction of amino acid taken up by the cells that was recovered free intracellularly, and therefore the concentration ratio (between intracellular water and medium), was enhanced by the hormone only with glycine, proline, serine, threonine, histidine and methionine. When isolated heart cells were incubated in the presence of a mixture of labelled amino acids, the addition of insulin increased the disappearance of radioactivity from the medium. 5. The general pattern of amino acid transport (in the absence and in the presence of insulin) in isolated cardiac cells was similar to that found in intact hearts, suggesting that the biological preparation described in this paper might be useful for studies of cell permeability and insulin action.

Corticosteroids and accumulation of C14-labeled amino acids and histamine by isolated rat diaphragm

1960 ◽  
Vol 199 (4) ◽  
pp. 715-718 ◽  
Author(s):  
Ira G. Wool
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Rat Diaphragm ◽  
Amino Acid Analogue ◽  
Rate Of Penetration ◽  
Aminoisobutyric Acid ◽  
Acid Analogue ◽  
Isolated Rat

The rate of penetration and the magnitude of accumulation of several utilized C14-amino acids, of the amino acid analogue, α-aminoisobutyric acid-1-C14, and of C14-histamine was measured in intact and cut isolated rat diaphragm. Adrenalectomy was without effect on the rate of entry of the amino acids or of histamine; cortisone administration (2 mg/day) depressed the accumulation of the utilized amino acids, of α-aminoisobutyric acid and of histamine.

scholarly journals Non-metabolizable amino acids are potent stimulators of hepatic and renal ornithine decarboxylase activity

1983 ◽  
Vol 210 (2) ◽  
pp. 617-619 ◽  
Author(s):  
E W Chideckel ◽  
D Edwards
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Protein Meal ◽  
Aminoisobutyric Acid ◽  
Ornithine Decarboxylase Activity

The non-metabolizable amino acids alpha-aminoisobutyric acid (AIB) and cycloleucine and the poorly metabolizable amino acid D-alanine potently stimulated hepatic ornithine decarboxylase (ODC) activity in starved rats. The stimulation by AIB was shown to have several of the characteristics of stimulation by a protein meal and occurred in hypophysectomized animals. AIB also stimulated renal, but not brain or heart, ODC activity.

scholarly journals Thermostable D-amino acid decarboxylases derived from Thermotoga maritima diaminopimelate decarboxylase

2021 ◽  
Vol 34 ◽  
Author(s):  
Antonija Marjanovic ◽  
Carlos J Ramírez-Palacios ◽  
Marcelo F Masman ◽  
Jeroen Drenth ◽  
Marleen Otzen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Building Block ◽  
Catalytic Properties ◽  
Thermotoga Maritima ◽  
Aminocaproic Acid ◽  
Biosynthetic Pathways ◽  
Catalytic Activities ◽  
The Common ◽  
Diaminopimelate Decarboxylase

Abstract Diaminopimelate decarboxylases (DAPDCs) are highly selective enzymes that catalyze the common final step in different lysine biosynthetic pathways, i.e. the conversion of meso-diaminopimelate (DAP) to L-lysine. We examined the modification of the substrate specificity of the thermostable decarboxylase from Thermotoga maritima with the aim to introduce activity with 2-aminopimelic acid (2-APA) since its decarboxylation leads to 6-aminocaproic acid (6-ACA), a building block for the synthesis of nylon-6. Structure-based mutagenesis of the distal carboxylate binding site resulted in a set of enzyme variants with new activities toward different D-amino acids. One of the mutants (E315T) had lost most of its activity toward DAP and primarily acted as a 2-APA decarboxylase. We next used computational modeling to explain the observed shift in catalytic activities of the mutants. The results suggest that predictive computational protocols can support the redesign of the catalytic properties of this class of decarboxylating PLP-dependent enzymes.

Amino acids of Hymenolepis palmarum (Johri, 1956) and chemotaxonomic studies on hymenolepidid cestodes

1985 ◽  
Vol 59 (1) ◽  
pp. 39-42 ◽  
Author(s):  
Anjali Bhalya ◽  
Amita Seth ◽  
Sandeep K. Malhotra ◽  
V. N. Capoor
Keyword(s):  
Amino Acids ◽  
Aminoisobutyric Acid ◽  
Qualitative And Quantitative ◽  
The Common

ABSTRACTChemotaxonomic patterns in the distribution of amino acids of Hymenolepis palmarum (Jouri, 1956) and other hymenolepidids revealed the common presence of β-aminoisobutyric acid, lysine, phcnylalaninc and tyrosine but 3,4 dihydroxyphenylalanine and norleucine were exclusive to H. palmarum. Both qualitative and quantitative differences in amino acids have been recorded.

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