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1.
Synthesis and Conformational Analysis of Cyclic Homooligomers from Pyranoid ε‐Sugar Amino Acids 下载免费PDF全文
Dr. Andrés Feher‐Voelger Jorge Borges‐González Dr. Romen Carrillo Dr. Ezequiel Q. Morales Dr. Javier González‐Platas Dr. Tomás Martín 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(14):4007-4022
New pyranoid ε‐sugar amino acids were designed as building blocks, in which the carboxylic acid and the amine groups were placed in positions C2 and C3 with respect to the tetrahydropyran oxygen atom. By using standard solution‐phase coupling procedures, cyclic homooligomers containing pyranoid ε‐sugar amino acids were synthesized. Conformation analysis was performed by using NMR spectroscopic experiments, FTIR spectroscopic studies, X‐ray analysis, and a theoretical conformation search. These studies reveal that the presence of a methoxy group in the position C4 of the pyran ring produces an important structural change in the cyclodipeptides. When the methoxy groups are present, the structure collapses through interresidue hydrogen bonds between the oxygen atoms of the pyran ring and the amide protons. However, when the cyclodipeptide lacks the methoxy groups, a U‐shape structure is adopted, in which there is a hydrophilic concave face with four oxygen atoms and two amide protons directed toward the center of the cavity. Additionally, we found important evidence of the key role played by weak electrostatic interactions, such as the five‐membered hydrogen‐bonded pseudocycles (C5) between the amide protons and the ether oxygen atoms, in the conformation equilibrium of the macrocycles and in the cyclization step of the cyclic tetrapeptides. 相似文献
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Yu‐Hui Zhang Prof. Dr. Kesheng Song Dr. Nian‐Yong Zhu Dr. Dan Yang Prof. Dr. 《Chemistry (Weinheim an der Bergstrasse, Germany)》2010,16(2):577-587
As a new type of foldamer, β‐aminoxy peptides have the ability to adopt novel β N? O turns or β N? O helices in solution. Herein, we describe a new subclass of β‐aminoxy peptide, that is, peptides of acyclic β2, 3‐aminoxy acids (NH2OCHR1CHR2COOH), in which the presence of two chiral centers provides insight into the effect of backbone stereochemistry on the folding of β‐aminoxy peptides. Acyclic β2, 3‐aminoxy peptides with syn and anti configurations have been synthesized and their conformations investigated by NMR, IR, and circular dichroism (CD) spectroscopic, and X‐ray crystallographic analysis. The β N? O turns or β N? O helices, which feature nine‐membered rings with intramolecular hydrogen bonds and have been identified previously in peptides of β3‐ and β2, 2‐aminoxy acids, are also predominantly present in the acyclic β2, 3‐aminoxy peptides with a syn configuration and N? O bonds gauche to the Cα? Cβ bonds in both solution and the solid state. In the acyclic β2, 3‐aminoxy peptides with an anti configuration, an extended strand (i.e., non‐hydrogen‐bonded state) is found in the solid state, and several conformations including non‐hydrogen‐bonded and intramolecular hydrogen‐bonded states are present simultaneously in nonpolar solvents. These results suggest that the backbone stereochemistry does affect the folding of the acyclic β2, 3‐aminoxy peptides. Theoretical calculations on the conformations of model acyclic β2, 3‐aminoxy peptides with different backbone stereochemistry were also conducted to elucidate structural characteristics. Our present work may provide useful guidelines for the design and construction of new foldamers with predicable structures. 相似文献
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Induced Folding of Protein‐Sized Foldameric β‐Sandwich Models with Core β‐Amino Acid Residues 下载免费PDF全文
Gábor Olajos Dr. Anasztázia Hetényi Dr. Edit Wéber Lukács J. Németh Dr. Zsolt Szakonyi Prof. Dr. Ferenc Fülöp Prof. Dr. Tamás A. Martinek 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(16):6173-6180
The mimicry of protein‐sized β‐sheet structures with unnatural peptidic sequences (foldamers) is a considerable challenge. In this work, the de novo designed betabellin‐14 β‐sheet has been used as a template, and α→β residue mutations were carried out in the hydrophobic core (positions 12 and 19). β‐Residues with diverse structural properties were utilized: Homologous β3‐amino acids, (1R,2S)‐2‐aminocyclopentanecarboxylic acid (ACPC), (1R,2S)‐2‐aminocyclohexanecarboxylic acid (ACHC), (1R,2S)‐2‐aminocyclohex‐3‐enecarboxylic acid (ACEC), and (1S,2S,3R,5S)‐2‐amino‐6,6‐dimethylbicyclo[3.1.1]heptane‐3‐carboxylic acid (ABHC). Six α/β‐peptidic chains were constructed in both monomeric and disulfide‐linked dimeric forms. Structural studies based on circular dichroism spectroscopy, the analysis of NMR chemical shifts, and molecular dynamics simulations revealed that dimerization induced β‐sheet formation in the 64‐residue foldameric systems. Core replacement with (1R,2S)‐ACHC was found to be unique among the β‐amino acid building blocks studied because it was simultaneously able to maintain the interstrand hydrogen‐bonding network and to fit sterically into the hydrophobic interior of the β‐sandwich. The novel β‐sandwich model containing 25 % unnatural building blocks afforded protein‐like thermal denaturation behavior. 相似文献
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Krishnayan Basuroy Appavu Rajagopal Dr. Srinivasarao Raghothama Prof. Narayanaswamy Shamala Prof. Padmanabhan Balaram 《化学:亚洲杂志》2012,7(7):1671-1678
The effect of gem‐dialkyl substituents on the backbone conformations of β‐amino acid residues in peptides has been investigated by using four model peptides: Boc‐Xxx‐β2,2Ac6c(1‐aminomethylcyclohexanecarboxylic acid)‐NHMe (Xxx=Leu ( 1 ), Phe ( 2 ); Boc=tert‐butyloxycarbonyl) and Boc‐Xxx‐β3,3Ac6c(1‐aminocyclohexaneacetic acid)‐NHMe (Xxx=Leu ( 3 ), Phe ( 4 )). Tetrasubstituted carbon atoms restrict the ranges of stereochemically allowed conformations about flanking single bonds. The crystal structure of Boc‐Leu‐β2,2Ac6c‐NHMe ( 1 ) established a C11 hydrogen‐bonded turn in the αβ‐hybrid sequence. The observed torsion angles (α(?≈?60°, ψ≈?30°), β(?≈?90°, θ≈60°, ψ≈?90°)) corresponded to a C11 helical turn, which was a backbone‐expanded analogue of the type III β turn in αα sequences. The crystal structure of the peptide Boc‐Phe‐β3,3Ac6c‐NHMe ( 4 ) established a C11 hydrogen‐bonded turn with distinctly different backbone torsion angles (α(?≈?60°, ψ≈120°), β(?≈60°, θ≈60°, ψ≈?60°)), which corresponded to a backbone‐expanded analogue of the type II β turn observed in αα sequences. In peptide 4 , the two molecules in the asymmetric unit adopted backbone torsion angles of opposite signs. In one of the molecules, the Phe residue adopted an unfavorable backbone conformation, with the energetic penalty being offset by a favorable aromatic interaction between proximal molecules in the crystal. NMR spectroscopy studies provided evidence for the maintenance of folded structures in solution in these αβ‐hybrid sequences. 相似文献
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Dr. Victoria Peddie Prof. Raymond J. Butcher Prof. Ward T. Robinson Prof. Matthew C. J. Wilce Dr. Daouda A. K. Traore Prof. Andrew D. Abell 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(21):6655-6662
Experimental and theoretical data indicate that, for α‐fluoroamides, the F? C? C(O)? N(H) moiety adopts an antiperiplanar conformation. In addition, a gauche conformation is favoured between the vicinal C? F and C? N(CO) bonds in N‐β‐fluoroethylamides. This study details the synthesis of a series of fluorinated β‐peptides ( 1 – 8 ) designed to use these stereoelectronic effects to control the conformation of β‐peptide bonds. X‐ray crystal structures of these compounds revealed the expected conformations: with fluorine β to a nitrogen adopting a gauche conformation, and fluorine α to a C?O group adopting an antiperiplanar conformation. Thus, the strategic placement of fluorine can control the conformation of a β‐peptide bond, with the possibility of directing the secondary structures of β‐peptides. 相似文献
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Back Cover: Induced Folding of Protein‐Sized Foldameric β‐Sandwich Models with Core β‐Amino Acid Residues (Chem. Eur. J. 16/2015) 下载免费PDF全文
Gábor Olajos Dr. Anasztázia Hetényi Dr. Edit Wéber Lukács J. Németh Dr. Zsolt Szakonyi Prof. Dr. Ferenc Fülöp Prof. Dr. Tamás A. Martinek 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(16):6304-6304
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Shaoquan Lin Dr. Naoya Kumagai Prof. Dr. Masakatsu Shibasaki 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(10):3296-3299
We report a direct catalytic asymmetric Mannich‐type addition of α,β‐unsaturated γ‐butyrolactam to α‐ethoxycarbonyl ketimines promoted by a soft Lewis acid/Brønsted base cooperative catalyst. A thiophosphinoyl group on the nitrogen of ketimines was crucial for both electrophilic activation and α‐addition of γ‐butyrolactams. The obtained aza‐Morita–Baylis–Hillman‐type products bear an α‐amino acid architecture with a tetra‐substituted stereogenic center. 相似文献
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Dr. Sara Pellegrino Dr. Alessandro Contini Prof. Francesca Clerici Dr. Alessandro Gori Donatella Nava Prof. Maria Luisa Gelmi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(28):8705-8715
A very efficient synthesis of orthogonally protected 1H‐azepine‐4‐amino‐4‐carboxylic acid, abbreviated as Azn, a conformationally restricted analogue of ornithine, was realized. It was obtained on a gram scale in good overall yield in five steps, three of which did not require isolation of the intermediates, starting from the readily available 1‐amino‐4‐oxo‐cyclohexane‐4‐carboxylic acid. Both enantiomers were used for the preparation of pentapeptide models containing Ala, Aib, and Azn. Conformational studies using both spectroscopic techniques (NMR, CD) and molecular dynamics on model 5‐mer peptides showed that the (R)‐Azn isomer possesses a marked helicogenic effect. 相似文献
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Gangavaram V. M. Sharma Dr. Kota Sudhakar Rao Rapolu Ravi Kongari Narsimulu Pendem Nagendar Chirutha Chandramouli Singarapu Kiran Kumar Ajit C. Kunwar Dr. 《化学:亚洲杂志》2009,4(1):181-193
The design and synthesis of β‐peptides from new C‐linked carbo‐β‐amino acids (β‐Caa) presented here, provides an opportunity to understand the impact of carbohydrate side chains on the formation and stability of helical structures. The β‐amino acids, Boc‐(S)‐β‐Caa(g)‐OMe 1 and Boc‐(R)‐β‐Caa(g)‐OMe 2 , having a D ‐galactopyranoside side chain were prepared from D ‐galactose. Similarly, the homo C‐linked carbo‐β‐amino acids (β‐hCaa); Boc‐(S)‐β‐hCaa(x)‐OMe 3 and Boc‐(R)‐β‐hCaa(x)‐OMe 4 , were prepared from D ‐glucose. The peptides derived from the above monomers were investigated by NMR, CD, and MD studies. The β‐peptides, especially the shorter ones obtained from the epimeric (at the amine stereocenter Cβ) 1 and 2 by the concept of alternating chirality, showed a much smaller propensity to form 10/12‐helices. This substantial destabilization of the helix could be attributed to the bulkier D ‐galactopyranoside side chain. Our efforts to prepare peptides with alternating 3 and 4 were unsuccessful. However, the β‐peptides derived from alternating geometrically heterochiral (at Cβ) 4 and Boc‐(R)‐β‐Caa(x)‐OMe 5 (D ‐xylose side chain) display robust right‐handed 10/12‐helices, while the mixed peptides with alternating 4 and Boc‐β‐hGly‐OMe 6 (β‐homoglycine), resulted in left‐handed β‐helices. These observations show a distinct influence of the side chains on helix formation as well as their stability. 相似文献
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Dr. Julie L. H. Madsen Dr. Claudia U. Hjørringgaard Dr. Brian S. Vad Prof. Dr. Daniel Otzen Prof. Dr. Troels Skrydstrup 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(24):8358-8367
Incorporation of silicon‐containing amino acids in peptides is known to endow the peptide with desirable properties such as improved proteolytic stability and increased lipophilicity. In the presented study, we demonstrate that incorporation of β‐silicon‐β3‐amino acids into the antimicrobial peptide alamethicin provides the peptide with improved membrane permeabilizing properties. A robust synthetic procedure for the construction of β‐silicon‐β3‐amino acids was developed and the amino acid analogues were incorporated into alamethicin at different positions of the hydrophobic face of the amphipathic helix by using SPPS. The incorporation was shown to provide up to 20‐fold increase in calcein release as compared with wild‐type alamethicin. 相似文献
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《Chemical record (New York, N.Y.)》2018,18(3):266-281
Fluorine‐containing organic molecules have generated increasing impact in drug research over the past decade. Their preparation and development of novel synthetic methods towards new types of fluorinated molecules among them of β‐amino acid derivatives has received large interest. Our research group have designed various highly selective and stereocontrolled methods for the construction of fluorine‐containing cyclic β‐amino acid derivatives. The synthetic approaches developed for the synthesis of various pharmacologically interesting cyclic β‐amino acid derivatives as monomers with multiple stereogenic centers might be valuable protocols for the access of other classes of organic compounds. 相似文献
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Synthesis and Conformational Analysis of Hybrid α/β‐Dipeptides Incorporating S‐Glycosyl‐β2,2‐Amino Acids 下载免费PDF全文
Iván García‐González Dr. Lara Mata Dr. Francisco Corzana Dr. Gonzalo Jiménez‐Osés Prof. Alberto Avenoza Dr. Jesús H. Busto Prof. Jesús M. Peregrina 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(3):1156-1168
We synthesized and carried out the conformational analysis of several hybrid dipeptides consisting of an α‐amino acid attached to a quaternary glyco‐β‐amino acid. In particular, we combined a S‐glycosylated β2,2‐amino acid and two different types of α‐amino acid, namely, aliphatic (alanine) and aromatic (phenylalanine and tryptophan) in the sequence of hybrid α/β‐dipeptides. The key step in the synthesis involved the ring‐opening reaction of a chiral cyclic sulfamidate, inserted in the peptidic sequence, with a sulfur‐containing nucleophile by using 1‐thio‐β‐D ‐glucopyranose derivatives. This reaction of glycosylation occurred with inversion of configuration at the quaternary center. The conformational behavior in aqueous solution of the peptide backbone and the glycosidic linkage for all synthesized hybrid glycopeptides was analyzed by using a protocol that combined NMR experiments and molecular dynamics with time‐averaged restraints (MD‐tar). Interestingly, the presence of the sulfur heteroatom at the quaternary center of the β‐amino acid induced θ torsional angles close to 180° (anti). Notably, this value changed to 60° (gauche) when the peptidic sequence displayed aromatic α‐amino acids due to the presence of CH–π interactions between the phenyl or indole ring and the methyl groups of the β‐amino acid unit. 相似文献
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Dr. Yosuke Demizu Prof. Mitsunobu Doi Dr. Masaaki Kurihara Prof. Tokumi Maruyama Prof. Hiroshi Suemune Prof. Masakazu Tanaka 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(8):2430-2439
Chiral cyclic α,α‐disubstituted amino acids, (3S,4S)‐ and (3R,4R)‐1‐amino‐3,4‐(dialkoxy)cyclopentanecarboxylic acids ((S,S)‐ and (R,R)‐Ac5cdOR; R: methyl, methoxymethyl), were synthesized from dimethyl L ‐(+)‐ or D ‐(?)‐tartrate, and their homochiral homoligomers were prepared by solution‐phase methods. The preferred secondary structure of the (S,S)‐Ac5cdOMe hexapeptide was a left‐handed (M) 310 helix, whereas those of the (S,S)‐Ac5cdOMe octa‐ and decapeptides were left‐handed (M) α helices, both in solution and in the crystal state. The octa‐ and decapeptides can be well dissolved in pure water and are more α helical in water than in 2,2,2‐trifluoroethanol solution. The left‐handed (M) helices of the (S,S)‐Ac5cdOMe homochiral homopeptides were exclusively controlled by the side‐chain chiral centers, because the cyclic amino acid (S,S)‐Ac5cdOMe does not have an α‐carbon chiral center but has side‐chain γ‐carbon chiral centers. 相似文献
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Tanaka M Nishimura S Oba M Demizu Y Kurihara M Suemune H 《Chemistry (Weinheim an der Bergstrasse, Germany)》2003,9(13):3082-3090
Optically active peptide foldamers Tfa-[(S)-(alphaEt)Leu]-[(S)-(alphaEt)Nva]-Deg-[(S)-(alphaEt)Nle]-OEt (10) and Tfa-[(S)-(alphaEt)Val]-[(S)-(alphaEt)Leu]-[(S)-(alphaEt)Nva]-Deg-[(S)-(alphaEt)Nle]-OEt (11) composed of diverse alpha-ethylated alpha,alpha-disubstituted alpha-amino acids were synthesized. The dominant conformation of these peptides in solution was an unusual, fully extended planar conformation, and that in the crystal state was both right-handed (P) and left-handed (M) 3(10)-helical structures in 10 and a P 3(10)-helical structure in 11, respectively. The preferred planar C(5) conformation of the peptides prepared from chiral alpha-ethylated alpha,alpha-disubstituted alpha-amino acids was drastically different from the 3(10)-helical structure of the peptides prepared from chiral alpha-methylated alpha,alpha-disubstituted alpha-amino acids. 相似文献