scholarly journals Rapid and scalable synthesis of innovative unnatural α,β or γ-amino acids functionalized with tertiary amines on their side-chains

2015 ◽  
Vol 13 (25) ◽  
pp. 7020-7026 ◽  
Author(s):  
Séverine Schneider ◽  
Hussein Ftouni ◽  
Songlin Niu ◽  
Martine Schmitt ◽  
Frédéric Simonin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Side Chain ◽  
Side Chains ◽  
Tertiary Amines ◽  
Scalable Synthesis ◽  
Tertiary Amides

We report a selective ruthenium catalyzed reduction of tertiary amides on the side chain of Fmoc-Gln-OtBu derivatives, leading to innovative unnatural α,β or γ-amino acids functionalized with tertiary amines.

scholarly journals Unexpected Trends in the Hydrophobicity of Fluorinated Amino Acids Reflect Competing Changes in Polarity and Conformation

2018 ◽  
Author(s):  
João R. Robalo ◽  
Ana Vila Verde
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Side Chain ◽  
Side Chains ◽  
Hydration Free Energy ◽  
Crossover Point ◽  
Fluorinated Amino Acids ◽  
Road Map ◽  
Alkyl Side Chains ◽  
The Impact

<div><div><div><p>Fluorination can dramatically improve the thermal and proteolytic stability of proteins and their enzymatic activity. Key to the impact of fluorination on protein properties is the hydrophobicity of fluorinated amino acids. We use molecular dynamics simulations, together with a new fixed-charge, atomistic force field, to quantify the changes in hydration free energy for amino acids with alkyl side chains and with 1 to 6 –CH to –CF side chain substitutions. Fluorination changes the hydration free energy by 1.5 to +2 kcal mol<sup>-</sup>1, but the number of fluorines is a poor predictor of hydrophobicity. Changes in hydration free energy reflect two main contributions: i) fluorination alters side chain-water interactions; we identify a crossover point from hydrophilic to hydrophobic fluoromethyl groups which may be used to estimate the hydrophobicity of fluorinated alkyl side-chains; ii) fluorination alters the number of backbone-water hydrogen bonds via changes in the relative side chain-backbone conformation. Our results offer a road map to mechanistically understand how fluorination alters hydrophobicity of (bio)polymers.</p></div></div></div>

A phase transition from monoclinicC2 withZ′ = 1 to triclinicP1 withZ′ = 4 for the quasiracemateL-2-aminobutyric acid–D-methionine (1/1)

2016 ◽  
Vol 72 (7) ◽  
pp. 536-543 ◽  
Author(s):  
Carl Henrik Görbitz ◽  
David S. Wragg ◽  
Ingrid Marie Bergh Bakke ◽  
Christian Fleischer ◽  
Gaute Grønnevik ◽  
...  
Keyword(s):  
Phase Transition ◽  
Amino Acids ◽  
Room Temperature ◽  
Aminobutyric Acid ◽  
Side Chain ◽  
Side Chains ◽  
Significant Difference ◽  
Hydrophobic Amino Acids ◽  
Chain Conformations ◽  
Triclinic Form

Racemates of hydrophobic amino acids with linear side chains are known to undergo a unique series of solid-state phase transitions that involve sliding of molecular bilayers upon heating or cooling. Recently, this behaviour was shown to extend also to quasiracemates of two different amino acids with opposite handedness [Görbitz & Karen (2015).J. Phys. Chem. B,119, 4975–4984]. Previous investigations are here extended to an L-2-aminobutyric acid–D-methionine (1/1) co-crystal, C4H9NO2·C5H11NO2S. The significant difference in size between the –CH2CH3and –CH2CH2SCH3side chains leads to extensive disorder at room temperature, which is essentially resolved after a phase transition at 229 K to an unprecedented triclinic form where all four D-methionine molecules in the asymmetric unit have different side-chain conformations and all three side-chain rotamers are used for the four partner L-2-aminobutyric acid molecules.

scholarly journals Unexpected Trends in the Hydrophobicity of Fluorinated Amino Acids Reflect Competing Changes in Polarity and Conformation

2018 ◽  
Author(s):  
João R. Robalo ◽  
Ana Vila Verde
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Side Chain ◽  
Side Chains ◽  
Hydration Free Energy ◽  
Crossover Point ◽  
Fluorinated Amino Acids ◽  
Road Map ◽  
Alkyl Side Chains ◽  
The Impact

<div><div><div><p>Fluorination can dramatically improve the thermal and proteolytic stability of proteins and their enzymatic activity. Key to the impact of fluorination on protein properties is the hydrophobicity of fluorinated amino acids. We use molecular dynamics simulations, together with a new fixed-charge, atomistic force field, to quantify the changes in hydration free energy for amino acids with alkyl side chains and with 1 to 6 –CH to –CF side chain substitutions. Fluorination changes the hydration free energy by 1.5 to +2 kcal mol<sup>-</sup>1, but the number of fluorines is a poor predictor of hydrophobicity. Changes in hydration free energy reflect two main contributions: i) fluorination alters side chain-water interactions; we identify a crossover point from hydrophilic to hydrophobic fluoromethyl groups which may be used to estimate the hydrophobicity of fluorinated alkyl side-chains; ii) fluorination alters the number of backbone-water hydrogen bonds via changes in the relative side chain-backbone conformation. Our results offer a road map to mechanistically understand how fluorination alters hydrophobicity of (bio)polymers.</p></div></div></div>

Gram-Scale Solution-Phase Synthesis of Heptapeptide Side Chain of Teixobactin

Synlett ◽  
2019 ◽  
Vol 30 (20) ◽  
pp. 2268-2272 ◽  
Author(s):  
Sangeetha Donikela ◽  
Kiranmai Nayani ◽  
Vishnuvardhan Nomula ◽  
Prathama S. Mainkar ◽  
Srivari Chandrasekhar
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Natural Product ◽  
Solution Phase ◽  
Side Chain ◽  
Phase Synthesis ◽  
Solution Phase Synthesis ◽  
Efficient Coupling ◽  
Scalable Synthesis

We report herein a scalable synthesis of linear heptapeptide side chain of the depsipeptide natural product teixobactin through solution phase. The synthesis of heptapeptide was achieved through an efficient coupling of suitably protected tripeptide and tetrapeptide comprising of three d-amino acids and four usual l-amino acid subunits.

scholarly journals Temperature-induced phase transitions for amino acids with linear side chains

2014 ◽  
Vol 70 (a1) ◽  
pp. C170-C170
Author(s):  
Carl Henrik Görbitz ◽  
Pavel Karen ◽  
Michal Dusek ◽  
Václav Petříček
Keyword(s):  
Amino Acids ◽  
Low Temperature ◽  
Side Chain ◽  
Side Chains ◽  
Ambient Conditions ◽  
Short Side ◽  
Space Groups ◽  
Cell Parameters ◽  
Commensurate Phase ◽  
Chain Conformations

Two polymorphs are known to exist under ambient conditions for a number of amino acids (three for glycine). While investigations at high pressure have revealed a number of additional polymorphs, temperature-induced changes are rare. Low-temperature structures with modified side-chain conformations were identified for L- and DL-cysteine. Furthermore, racemates with linear side chains, such as DL-methionine and the non-standard DL-aminobutyric acid (DL-Abu), DL-aminopentanoic acid (DL-norvaline, DL-Nva) and DL-aminohexanoic acid (DL-norleucine, DL-Nle), undergo major crystalline rearrangements on transitions between P21/c and C2/c space groups [1], some of them entropy driven (disordering). As for the corresponding enantio-pure amino acids, we recently described related P21 and I2 structures at 105 K for L-Abu, both with Z' = 4 [2]. A short side-chain C–C bond (1.426 Å) in the only available CSD entry for L-Nle (at 298 K) [3] lead us to suspect that disorder could have been overlooked in the original refinement. L-Nva has not been described previously. We now present single-crystal X-ray determinations between 105 and 405 K for L-Abu, L-Nva and L-Nle, showing phase behavior of unprecedented complexity. For L-Abu and L-Nva we find three different forms in this temperature interval, while four different phases were found for L-Nle. Its known C2 structure with Z' = 1 prevails between 200 and 390 K, and the side chain is indeed disordered 2:1 over two positions. Above 390 K disorder is extensive; the space group remains C2 but cell parameters change. Upon cooling new low-temperature forms are observed at 200 and 170 K. Both are modulated, but to a different extent: data collected at 100 K reveal an almost commensurate phase, while the 180 K phase is fully incommensurate. This is, to our knowledge, the first observation of modulated structures for an amino acid, and also the first observations of major crystalline rearrangements akin to those seen for the corresponding racemates.

Molecular aggregation in crystalline 1:1 complexes of hydrophobic D- and L-amino acids. I. The L-isoleucine series

1999 ◽  
Vol 55 (3) ◽  
pp. 424-431 ◽  
Author(s):  
Bjørn Dalhus ◽  
Carl Henrik Görbitz
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Aminobutyric Acid ◽  
Side Chain ◽  
Side Chains ◽  
Amino Acid Side Chain ◽  
Molecular Aggregation ◽  
Plane Symmetry ◽  
Hydrogen Bond Pattern ◽  
Polar Parts

The amino acid L-isoleucine has been cocrystallized with seven selected D-amino acids including D-methionine [L-isoleucine–D-methionine (1/1), C6H13NO2.C5H11NO2S, amino-acid side chain R = —CH2—CH2—S—CH3] and a homologous series from D-alanine [L-isoleucine–D-alanine (1/1), C6H13NO2.C3H7NO2, R = —CH3] through D-α-aminobutyric acid [L-isoleucine–D-α-aminobutyric acid (1/1), C6H13NO2.C4H9NO2, R = —CH2—CH3] and D-norvaline [L-isoleucine–D-norvaline (1/1), C6H13NO2.C5H11NO2, R = —CH2—CH2—CH3] to D-norleucine [L-isoleucine–D-norleucine (1/1), C6H13NO2.C6H13NO2, R = —CH2—CH2—CH2—CH3] with linear side chains, and D-valine [L-isoleucine–D-valine (1/1), C6H13NO2.C5H11NO2, R = —CH—(CH3)2] and D-leucine [L-isoleucine–D-leucine (1/1), C6H13NO2.C6H13NO2, R = —CH2—CH—(CH3)2] with branched side chains. All the crystal structures are divided into distinct hydrophilic and hydrophobic layers. In the five complexes with amino acids with linear side chains the polar parts of the D- and L-amino acids are related by pseudo-glide-plane symmetry, and four of them have remarkably similar molecular arrangements. The D-valine and D-leucine complexes, on the other hand, are structurally quite different with the polar parts of the D- and L-amino acids related by pseudo-inversion. Differences in the hydrogen-bond pattern in the two molecular arrangements are discussed.

Synthesis and evaluation of chiral β-amino acid-based low-molecular-weight organogelators possessing a methyl/trifluoromethyl side chain

2019 ◽  
Vol 43 (7) ◽  
pp. 2882-2887 ◽  
Author(s):  
Koichi Kodama ◽  
Ryuta Kawamata ◽  
Takuji Hirose
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Amino Acid ◽  
Supramolecular Structures ◽  
Side Chain ◽  
Low Molecular Weight ◽  
Side Chains ◽  
Low Molecular Weight Organogelators

Impacts of side-chains and chirality of organogelators derived from β-amino acids are described with their supramolecular structures.

Constructing a Syntheses Table of the Standard Amino Acid Based on the PAM250 Matrix

2011 ◽  
Vol 335-336 ◽  
pp. 1279-1284
Author(s):  
Xiao Hong Shi ◽  
Xiang Hong Wang
Keyword(s):  
Amino Acids ◽  
Molecular Weight ◽  
Amino Acid ◽  
Physicochemical Properties ◽  
Side Chain ◽  
Side Chains ◽  
Chemical Structures ◽  
Naturally Occurring ◽  
Standard Amino Acid ◽  
Similar Amino Acid

It is well known that there are some similarities among various naturally occurring amino acids. The standard amino acids have been grouped by their general properties and the chemical structures of their side chains. In this paper we divided the molecular weight of amino acid into two parts: backbone molecular weight Mband side chain molecular weight Ms. We naturally grouped the amino acids into two sets according to the rate of Ms/ Mb. We developed a method to construct a syntheses table to reflect the relevant physicochemical properties based on the PAM250 matrix and successfully established an elegant table of the twenty amino acids. Our work proved that PAM250 matrix could be used not only in finding reasonable alignments but also in grouping similar amino acid.

scholarly journals An exceptional series of phase transitions in hydrophobic amino acids with linear side chains

IUCrJ ◽  
2016 ◽  
Vol 3 (5) ◽  
pp. 341-353 ◽  
Author(s):  
Carl Henrik Görbitz ◽  
Pavel Karen ◽  
Michal Dušek ◽  
Václav Petříček
Keyword(s):  
Amino Acids ◽  
Phase Transitions ◽  
Room Temperature ◽  
Side Chain ◽  
Side Chains ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Modulated Structure ◽  
Hydrogen Bond Pattern ◽  
Hydrophobic Amino Acids

The solid-state phase transitions and intermediate structures ofS-2-aminobutanoic acid (L-2-aminobutyric acid),S-2-aminopentanoic acid (L-norvaline),S-2-aminohexanoic acid (L-norleucine) and L-methionine between 100 and 470 K, identified by differential scanning calorimetry, have been characterized in a comprehensive single-crystal X-ray diffraction investigation. Unlike other enantiomeric amino acids investigated until now, this group featuring linear side chains displays up to five distinct phases. The multiple transitions between them involve a number of different processes: alteration of the hydrogen-bond pattern, to our knowledge the first example of this observed for an amino acid, sliding of molecular bilayers, seen previously only for racemates and quasiracemates, concerted side-chain rearrangements and abrupt as well as gradual modifications of the side-chain disorder. Ordering of L-norleucine upon cooling even proceedsviaan incommensurately modulated structure. L-Methionine has previously been described as being fully ordered at room temperature. An accurate refinement now reveals extensive disorder for both molecules in the asymmetric unit, while two previously unknown phases occur above room temperature.

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