Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• systems to study this disorder. The most common of these mouse models carries the SOD1 G93A mutation where glycine is substituted for alanine at position 93 in the superoxide dismutase 1 protein [6][7]. Other related mutations in SOD1 include H46R, A4V, and G85R. These mutations are not believed to reduce

• neuroblastoma-spinal cord (NSC)-34 cells, a motor neuron cell line [19]. Since D-serine serves as a co-agonist at the glycine site of the NMDA glutamate receptor, increases in D-serine are likely to contribute to glutamate excitotoxicity in ALS patients. These data suggest that reducing D-serine levels through

A peptidic hydrogel that may behave as a “Trojan Horse”

• Nicola Castellucci,
• Giorgio Sartor,
• Natalia Calonghi,
• Carola Parolin,
• Giuseppe Falini and
• Claudia Tomasini

Beilstein J. Org. Chem. 2013, 9, 417–424, doi:10.3762/bjoc.9.44

• and then fixed with 3% paraformaldehyde and washed with 0.1 M glycine in PBS and 1% BSA in PBS. Preparations were embedded in Mowiol, and the images were acquired by using sequential laser excitations at 488 nm. The images were collected by using a Nikon C1s confocal laser scanning microscope

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• water-soluble protein coating, which is necessary for the cell attachment. In this paper, we disclose a strategy to strongly attach ECs to TPX 2 membranes by covalent functionalization of the chemically rather inert material with a cyclic peptide, containing the RGD (arginine-glycine-asparagine) amino

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• , Wuhan 430070, China 10.3762/bjoc.9.30 Abstract The hydrochloride of the racemic amino acid (2-(7-hydroxycoumarin-4-yl)ethyl)glycine, which can serve as a fluorescent probe in proteins, and two halogen derivatives of it, were synthesized by using a new synthetic protocol in five steps. It is less costly

• ; Pechmann condensation; Introduction Since α-L-(2-(7-hydroxycoumarin-4-yl)ethyl)glycine (1a, Figure 1), a fluorescent non-natural amino acid, was genetically incorporated at a defined site in proteins in living organisms for the first time by Schultz and co-workers [1] there have been more and more

• coumarinylacetic acid, which was then reduced to an alcohol by borane-dimethyl sulfide. After the phenolic hydroxy group was protected with a tert-butyl(dimethyl)silyl group, the alcohol was converted into a bromide and was used to alkylate a glycine enolate synthon to afford an imine. All the protecting groups

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• modulatory binding site in a different manner than 2 and its analogues [33]. Possible support for such a hypothesis can be seen in the different activity profiles of α,α-disubstituted glycine analogues of PLG and the corresponding α,α-disubstituted derivatives of lactam PLG peptidomimetic 2 [35]. In addition

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• , glycine) and an important collaboration [18][19][20][21][22][23][24] between George Hess (a biophysicist) and Barry Carpenter (a chemist). Why was this collaboration important for this field? The answer has two parts. First, it is rare for one group to encompass all the expertise required for the

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• oligonucleotides [5][6][7][11][12][13] displaying only very little toxicity towards mammalian cells [11]. They have also been shown to function in the recognition of biomacromolecules. Likewise, other polycationic species, such as the N-alkylated glycine oligomers (peptoids) [14][15][16][17][18][19][20][21][22][23

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• . Alkylation of imine Alkylation of glycine imine by using a chiral phase-transfer catalyst emerged as a very good strategy for the asymmetric synthesis of amino-acid derivatives [59][60][61]. Lamaty and co-workers prepared a series of glycine Schiff bases 22 in excellent yield (97–98%) in short reaction time

• by milling protected glycine hydrochloride 21 and diphenylmethanimine (20), under solvent-free conditions (Scheme 11) [62]. The asymmetric alkylation of glycine imine 22 was carried out by using a phase-transfer catalyst under basic conditions in a ball-mill. The Schiff base reacted rapidly with

• Michael reaction assisted by pestle and mortar grinding. C-2 symmetric thiourea catalysed enantioselective MBH reaction. Quinine-catalysed ring opening of meso-anhydride by ball-milling. Ball-milling-assisted (A) synthesis of glycine schiff bases and (B) their organocatalytic asymmetric alkylation

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• ,2R,3R)-γ-chloro-α,β-diaminocarboxyl esters obtained via Mannich-type addition of analogous N-(diphenylmethylene)glycine esters across a chiral α-chloro-N-p-toluenesulfinylaldimine. Selective deprotection under different acidic reaction conditions and ring closure of the γ-chloro-α,β

• chemistry and is continuously under development [1][2][3]. Recently, our research group elaborated the asymmetric synthesis of new chiral γ-chloro-α,β-diaminocarboxyl esters by highly diastereoselective Mannich-type reactions of N-(diphenylmethylene)glycine esters across a chiral α-chloro-N-p

• ring closure and deprotection of the α-amino functionality of the synthesized γ-chloro-α,β-diaminocarboxylamides were explored as well. Results and Discussion The stereoselective synthesis of chiral γ-chloro-α,β-diaminocarboxylamides was performed by using a Mannich-type addition of glycine amides 4

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• to Grignard reagents that can be employed under aqueous conditions [58]. Initially, the α-photodecarboxylation of phthaloyl glycine 44 (Scheme 16) was investigated in a microflow Dwell device and compared with the reaction under batch conditions. The microflow reactor required a shorter residence

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

• Vadim A. Soloshonok,
• José Luis Aceña,
• Hisanori Ueki and
• Jianlin Han

Beilstein J. Org. Chem. 2012, 8, 1920–1928, doi:10.3762/bjoc.8.223

• framework of our recently described methodology for applying a new generation of nucleophilic glycine equivalents [27][28][29][30][31][32] to a general asymmetric synthesis of α-amino acids [33][34][35][36][37][38]. In this manner, modular assembly of achiral C2-symmetric pentadentate ligands 12 was carried

• compounds 12 with glycine. As shown in Scheme 4, heating of pentadentate ligands 12 in acetonitrile in the presence of a Ni(II) source [NiCl2 or Ni(NO3)2], glycine and a base, lead to the formation of the quite unusual complexes 14. In a similar manner, by using PdCl2 instead of Ni(II), the Pd-chelated

• complex 15 was obtained. As it follows from these results, only one carbonyl group in the starting ligands 12 was involved in the formation of the corresponding Schiff base with glycine, similar to the reactivity observed for tridentate ligands with Ni(II) [49][50][51][52][53]. In the 1H and 13C NMR

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• site of gp120. Ionic interactions of R59 of CD4 with D368 of gp120 stabilize this interaction [3] (Figure 1). Mutation of F43 and R59 to alanine or glycine [11][12][13][14] dramatically impairs binding to gp120, corroborating the importance of F43 and R59 for the interaction of CD4 with gp120

Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• /DIC. Synthesis of branched (sC18)2 was achieved by N-terminal coupling of Dde-Lys(Fmoc)-OH to sC18(5-16) and subsequent automated elongation of the peptide chain at the lysine side chain by using Nα-Boc protected glycine at the terminal position. Cleavage of the Dde group was achieved by treatment

Asymmetric desymmetrization of meso-diols by C₂-symmetric chiral 4-pyrrolidinopyridines

• Hartmut Schedel,
• Keizo Kan,
• Yoshihiro Ueda,
• Kenji Mishiro,
• Keisuke Yoshida,
• Takumi Furuta and
• Takeo Kawabata

Beilstein J. Org. Chem. 2012, 8, 1778–1787, doi:10.3762/bjoc.8.203

• and 8b with a D-tryptophan side chain gave (1R,2S)-6 [8] by asymmetric desymmetrization of 5, catalysts with achiral side chains were then examined. The acylation of 5 with catalyst 9 which possesses a tryptamine moiety gave 6 in 72% ee and 74% yield (Table 1, entry 3). Catalyst 10 with a glycine

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• of sequential mutations on the adsorption of such synthetic AFGP analogues onto ice surfaces, and to corroborate the molecular mechanism of antifreeze activity. Recently, we published the synthesis of monosaccharide-based AFGP analogues containing glycine, proline and serine instead of alanine

Synthetic studies towards bottromycin

• Stefanie Ackermann,
• Hans-Georg Lerchen,
• Dieter Häbich,
• Angelika Ullrich and
• Uli Kazmaier

Beilstein J. Org. Chem. 2012, 8, 1652–1656, doi:10.3762/bjoc.8.189

• . 3668-L2, named bottromycin A and B [13][14]. Acidic hydrolysis provided a mixture of all-(S)-configured amino acids containing 3-methylphenylalanine [15], tert-leucine, valine, β-(2-thiazolyl)-β-alanine [16] and glycine. While also proline was found in bottromycin B, cis-3-methylproline is a component

• endothiopeptide and ring closure between proline and glycine. The same group also undertook some modifications on the natural product [26]. Results and Discussion Our group is also involved in the synthesis of peptide-based natural products [27][28][29][30][31][32], and of course the structure of bottromycin is

Synthesis of conformationally restricted glutamate and glutamine derivatives from carbonylation of orthopalladated phenylglycine derivatives

• Esteban P. Urriolabeitia,
• Eduardo Laga and
• Carlos Cativiela

Beilstein J. Org. Chem. 2012, 8, 1569–1575, doi:10.3762/bjoc.8.179

• , and pure isolated compound 5 has been characterized as containing the NHTf group and two different CO2Me moieties, as represented in Scheme 5 (left). This result can be interpreted as a competing reaction between the nucleophilic abilities of the N atom of the glycine moiety and the oxygen atom of the

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters

• Takuya Uno,
• Yusuke Kobayashi and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2012, 8, 1499–1504, doi:10.3762/bjoc.8.169

• migration of the N-acyl glycine derivatives [18]. The other consists of C–N bond-forming reactions, such as (c) a rhodium-catalyzed N–H insertion reaction with α-diazo-β-keto esters [19][20][21], and (d) α-oxidation of β-keto esters to the corresponding oximes and the subsequent hydrogenation [22]. However

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• transformation of 1 to 5 indicates that 1 functions as a glycine enolate equivalent with the benzoylamino group in 5 being introduced in umpolung fashion (reaction involves the migration to an electrophilic nitrogen center). Hofmann rearrangement approach Our strategy was based on the known ethyl

• alkylation methodology has been co-opted to generate substitution α to the amino group, i.e., the (trioxaadamantyl)acetate 6 functions potentially as a glycine enolate equivalent. It is also noteworthy that, as the Hofmann rearrangement involves migration to electron-deficient nitrogen [10][11][12], the

Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• we had to place the ligation junction next to the third amino acid serine of the SKV binding motif. In the case of the conventional NCL, we used cysteine at the ligation site, and for the auxiliary mediated ligations, we decided to introduce auxiliary-glycine-conjugates at the N-terminus, due to the

• procedures (Supporting Information File 1) [4][17]. The syntheses of the auxiliary-linked glycine conjugates 7 and 8 were accomplished by using literature protocols developed by Dawson, Offer and MacMillan [7][8] (Figure 2). The Cys-peptide 3 and the Nα-auxiliary peptides 4 and 5 were assembled on Wang resin

• for the application in ligation studies. AMPB = (aminomethylphenylazo)benzoic acid. Structure of the glycine-linked auxiliary conjugates 7 and 8. Structural differences between the trans- and the cis-state of azopeptides with a SKV PDZ binding motif. Solid-phase synthesis of the ligation-mediating

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• ][29][30][31][32][33][34][35][36] or from screening of combinatorial libraries [37][38] have been reported. WGA is a 36 kDa plant lectin composed of two identical glycine- and cysteine-rich subunits [39] and is enriched in the seeds of Triticum vulgaris. It is specific for terminal N-acetylneuraminic

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• amine group is reduced resulting in longer coupling times and lower yields. Therefore, the auxiliary method is mainly applied when the ligation site contains a glycine residue. To avoid these limitations, a ligation methodology has been developed with the thiol group linked to the amino-acid side-chain

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• with the ECM. To characterize the affected interactions in more detail, cells were incubated with peptidic integrin ligands and GSF in combination. The RGD motif (an arginine–glycine–aspartic acid peptide sequence) is recognized and bound by several integrins including αvβ3 and α5β1. The sequence

• -containing peptide: glycine–arginine–glycine–aspartic acid–serine–proline (GRGDSP) or EILDV. Neither peptide, up to 2 mM, completely inhibited adhesion of WM-115 cells to fibronectin. We then decided to combine the peptidic integrin ligands with GSF to see if an antagonism or additive effect upon cell

Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

• Raheleh Rezaei Araghi,
• Carsten C. Mahrenholz,
• Rudolf Volkmer and
• Beate Koksch

Beilstein J. Org. Chem. 2012, 8, 640–649, doi:10.3762/bjoc.8.71

• positions relevant to coiled-coil binding were replaced with glycine. As depicted in Figure 3, both/either (i) hydrophobic (a15,d18) and/or electrostatic (e19,g21) positions of the central heptad or (ii) essential hydrophobic positions in the flanking heptads were substituted with glycine. This set of

• representatives). The second and third classes contain the mutants with SI values lower than those of the strong binders but still above 50% and 25% of that of Acid-pp, respectively. The poor binders have SI values below 25% of that of Acid-pp. This group also contains the aforementioned glycine-mutants. For each

• interact efficiently with B3β2γ. The glycine-scan (Figure 3) reveals the nature of the chimeric coiled-coil interaction. Only the acid-pp wt shows strong binding to B3β2γ. If the hydrophobic or electrostatic regions essential for coiled-coil binding are blocked by glycine, the signal breaks down. As

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22