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Open AccessArticle Development of Designed Site-Directed Pseudopeptide-Peptido-Mimetic Immunogens as Novel Minimal Subunit-Vaccine Candidates for Malaria

by José Manuel Lozano, Liliana P. Lesmes, Luisa F. Carreño, Gina M. Gallego and Manuel Elkin Patarroyo

Molecules 2010, 15(12), 8856-8889; https://doi.org/10.3390/molecules15128856

Received: 26 September 2010 / Accepted: 28 October 2010 / Published: 6 December 2010

Cited by 7 | PDF Full-text (1126 KB)

Abstract

Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies

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Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies for improving the immunogenicity properties of these sequences, the approach consisting of identifying high binding motifs present in those, and then performing specific changes on amino-acids belonging to such motifs, has proven to be a workable strategy. In addition, other strategies consisting of chemically introducing non-natural constraints to the backbone topology of the molecule and modifying the α-carbon asymmetry are becoming valuable tools to be considered in this pursuit. Non-natural structural constraints to the peptide backbone can be achieved by introducing peptide bond isosters such as reduced amides, partially retro or retro-inverso modifications or even including urea motifs. The second can be obtained by strategically replacing L-amino-acids with their enantiomeric forms for obtaining both structurally site-directed designed immunogens as potential vaccine candidates and their Ig structural molecular images, both having immuno-therapeutic effects for preventing and controlling malaria. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

Open AccessArticle Solid-Phase Synthesis and Evaluation of Glycopeptide Fragments from Rat Epididymal Cysteine-Rich Secretory Protein-1 (Crisp-1) ^‡

by Mian Liu, David W. Hamilton and George Barany

Molecules 2010, 15(9), 6399-6410; https://doi.org/10.3390/molecules15096399

Received: 17 May 2010 / Revised: 24 August 2010 / Accepted: 6 September 2010 / Published: 14 September 2010

Cited by 1 | PDF Full-text (282 KB)

Abstract

Three 18-residue peptides with the sequence Glp-Asp-Thr-Thr-Asp-Glu-Trp-Asp-Arg-Asp-Leu-Glu-Asn-Leu-Ser-Thr-Thr-Lys, taken from the N-terminus of the rat epididymal cysteine-rich secretory protein (Crisp-1) that is important in the fertilization process, were prepared by Fmoc solid-phase synthesis using a convergent strategy. These

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Three 18-residue peptides with the sequence Glp-Asp-Thr-Thr-Asp-Glu-Trp-Asp-Arg-Asp-Leu-Glu-Asn-Leu-Ser-Thr-Thr-Lys, taken from the N-terminus of the rat epididymal cysteine-rich secretory protein (Crisp-1) that is important in the fertilization process, were prepared by Fmoc solid-phase synthesis using a convergent strategy. These peptides were the parent sequence, plus two possible α-O-linked T_N antigen-containing glycopeptides with a Thr(α-D-GalNAc) residue in place of either Thr³ or Thr⁴. During chain assembly, two deletion peptides [des-Asp² and des-Thr(Ac₃-α-D-GalNAc)] and one terminated peptide [N-acetylated 14-mer] arose, as did several peptides in which aspartimide formation had occurred at each of the four possible positions in the sequence. These by-products totaled ~20% of the desired product; they were recognized by HPLC and ESI-MS and removed during the intermediate purifications. Final products, obtained in 15-21% overall yields, were characterized by HPLC purities and ESI-MS. Circular dichroism (CD) spectra for all three purified peptides, recorded in pure water and in trifluoroethanol-H₂O (1:1), revealed that the presence of a sugar moiety does not significantly impact the sampled conformations. Future biological evaluation could elucidate the nature and locus of sugar modification of Crisp-1, and provide insight as to why Crisp-1 protein E binds sperm irreversibly, in contrast to protein D that lacks a sugar near the N-terminus and only binds sperm loosely. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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Open AccessArticle Solid-Phase Synthesis of Oligodeoxynucleotides Containing N⁴-[2-(t-butyldisulfanyl)ethyl]-5-methylcytosine Moieties

by Sónia Pérez-Rentero, Alejandra V. Garibotti and Ramón Eritja

Molecules 2010, 15(8), 5692-5707; https://doi.org/10.3390/molecules15085692

Received: 28 May 2010 / Revised: 28 July 2010 / Accepted: 5 August 2010 / Published: 18 August 2010

Cited by 6 | PDF Full-text (253 KB) | Supplementary Files

Abstract

An efficient route for the synthesis of the phosphoramidite derivative of 5-methylcytosine bearing a tert-butylsulfanyl group protected thiol is described. This building block is used for the preparation of oligonucleotides carrying a thiol group at the nucleobase at the internal position of

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An efficient route for the synthesis of the phosphoramidite derivative of 5-methylcytosine bearing a tert-butylsulfanyl group protected thiol is described. This building block is used for the preparation of oligonucleotides carrying a thiol group at the nucleobase at the internal position of a DNA sequence. The resulting thiolated oligonucleotides are useful intermediates to generate oligonucleotide conjugates carrying molecules of interest at internal positions of a DNA sequence. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

Open AccessArticle Solid-Phase Synthetic Route to Multiple Derivatives of a Fundamental Peptide Unit

by William L. Scott, Ziniu Zhou, Paweł Zajdel, Maciej Pawłowski and Martin J. O’Donnell

Molecules 2010, 15(7), 4961-4983; https://doi.org/10.3390/molecules15074961

Received: 7 June 2010 / Revised: 23 June 2010 / Accepted: 12 July 2010 / Published: 20 July 2010

Cited by 4 | PDF Full-text (357 KB)

Abstract

Amino acids are Nature’s combinatorial building blocks. When substituted on both the amino and carboxyl sides they become the basic scaffold present in all peptides and proteins. We report a solid-phase synthetic route to large combinatorial variations of this fundamental scaffold, extending the

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Amino acids are Nature’s combinatorial building blocks. When substituted on both the amino and carboxyl sides they become the basic scaffold present in all peptides and proteins. We report a solid-phase synthetic route to large combinatorial variations of this fundamental scaffold, extending the variety of substituted biomimetic molecules available to successfully implement the Distributed Drug Discovery (D3) project. In a single solid-phase sequence, compatible with basic amine substituents, three-point variation is performed at the amino acid a-carbon and the amino and carboxyl functionalities. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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Open AccessArticle Solid-Phase Synthesis of New Trp(Nps)-Containing Dipeptide Derivatives as TRPV1 Channel Blockers

by Mª Jesús Pérez De Vega, Mª Teresa García-López, Laura Zaccaro, Miriam Royo, Fernando Albericio, Asia Fernández-Carvajal, Antonio Ferrer-Montiel and Rosario González-Muñiz

Molecules 2010, 15(7), 4924-4933; https://doi.org/10.3390/molecules15074924

Received: 11 June 2010 / Revised: 14 July 2010 / Accepted: 15 July 2010 / Published: 15 July 2010

Cited by 2 | PDF Full-text (248 KB)

Abstract

Trp(Nps)-Lys-NH₂ derivatives, bearing alkyl or guanidine groups either at the N–terminus or on the Lys side-chain or at both positions were conveniently prepared on solid-phase and evaluated as TRPV1 channel antagonists. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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Open AccessArticle Solid-Phase Synthesis of the Lipopeptide Myr-HBVpreS/2-78, a Hepatitis B Virus Entry Inhibitor

by Alexa Schieck, Thomas Müller, Andreas Schulze, Uwe Haberkorn, Stephan Urban and Walter Mier

Molecules 2010, 15(7), 4773-4783; https://doi.org/10.3390/molecules15074773

Received: 20 May 2010 / Revised: 2 July 2010 / Accepted: 5 July 2010 / Published: 7 July 2010

Cited by 9 | PDF Full-text (306 KB)

Abstract

Chronic HBV infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Synthetic peptides derived from the N-terminus of the large HBV envelope protein (L-protein) have been shown to efficiently block HBV entry. Myr-HBVpreS/2-78, the parent compound of these drugs,

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Chronic HBV infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Synthetic peptides derived from the N-terminus of the large HBV envelope protein (L-protein) have been shown to efficiently block HBV entry. Myr-HBVpreS/2-78, the parent compound of these drugs, inhibits human HBV infection in vitro and in vivo. An efficient synthesis is required, as these peptides constitute a novel class of anti HBV drugs. Consequently, the solid phase synthesis of the N-terminal 77 amino acids of the viral L-protein was studied in detail. The peptide was N-terminally myristoylated to resemble the natural, postranslationally modified protein. The synthesis was monitored using the Fmoc cleavage pattern of the solid phase synthesis on a standard peptide synthesizer and by LC-MS analyses of the arising side products. “Difficult sequences” in the positions 42-47 of the peptide sequence complicate the efficient synthesis of the 77-mer peptide HBVpreS/2-78. Attempts were undertaken to optimize the synthesis by heating, double coupling or the use of pseudoproline dipeptides. HPLC-MS analyses showed that the efficiency of the synthesis could be increased best by temperature elevation. This resulted in a higher purity of the crude product after solid phase synthesis. It was possible to minimize the occurrence of side products due to the positive effects related to higher reaction temperature. In conclusion, the peptide is accessible by stepwise SPPS without the necessity of segment coupling. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

Open AccessArticle Cell Proliferation of HaCaT Keratinocytes on Collagen Films Modified by Argon Plasma Treatment

by Jorge López García, Ahmad Asadinezhad, Jiří Pacherník, Marián Lehocký, Ita Junkar, Petr Humpolíček, Petr Sáha and Pavel Valášek

Molecules 2010, 15(4), 2845-2856; https://doi.org/10.3390/molecules15042845

Received: 22 January 2010 / Revised: 15 April 2010 / Accepted: 19 April 2010 / Published: 20 April 2010

Cited by 47 | PDF Full-text (2432 KB)

Abstract

Argon plasma treatment was used to modify the surface of atelocollagen films using a plasmochemical reactor. To evaluate the effects of the treatment, the untreated and treated samples were characterized by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM)

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Argon plasma treatment was used to modify the surface of atelocollagen films using a plasmochemical reactor. To evaluate the effects of the treatment, the untreated and treated samples were characterized by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM) imaging, and X-ray Photoelectron Spectroscopy (XPS) techniques. Cell growth was carried out by culturing human immortalized keratinocyte (HaCaT) cells and proliferation was measured via MTT assay. It was observed that argon plasma treatment significantly enhanced the extent of cell proliferation, which was ascribed to the favourable role of plasma treatment in inducing surface oxygen-containing entities together with increasing surface roughness. This can be considered as a potentially promising approach for tissue regeneration purposes. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

Open AccessArticle Solid-Phase Synthesis of Optically Active Substituted 2 Aminofuranones Using an Activated Carbonate Linker

by Dimitris Matiadis, Kyriakos C. Prousis and Olga Igglessi-Markopoulou

Molecules 2009, 14(10), 3914-3921; https://doi.org/10.3390/molecules14103914

Received: 8 September 2009 / Revised: 29 September 2009 / Accepted: 30 September 2009 / Published: 30 September 2009

Cited by 8 | PDF Full-text (204 KB)

Abstract

An efficient three-step solid-phase synthesis of diverse 3,5-disubstituted-2-aminofuranones has been developed. α-Hydroxy acids loaded on a nitrophenyl carbonate derivative of Wang resin are used as acylating agents for the C-acylation of active methylene compounds and the resulting intermediates provided, through a cyclative

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An efficient three-step solid-phase synthesis of diverse 3,5-disubstituted-2-aminofuranones has been developed. α-Hydroxy acids loaded on a nitrophenyl carbonate derivative of Wang resin are used as acylating agents for the C-acylation of active methylene compounds and the resulting intermediates provided, through a cyclative cleavage reaction, the desired product. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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Review

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Open AccessReview Solid-Phase Parallel Synthesis of Drug-Like Artificial 2H-Benzopyran Libraries

by Taeho Lee and Young-Dae Gong

Molecules 2012, 17(5), 5467-5496; https://doi.org/10.3390/molecules17055467

Received: 10 April 2012 / Revised: 25 April 2012 / Accepted: 7 May 2012 / Published: 9 May 2012

Cited by 18 | PDF Full-text (433 KB) | HTML Full-text | XML Full-text

Abstract

This review covers the construction of drug-like 2H-benzopyrans and related libraries using solid-phase parallel synthesis. In this context, the preparation of substituted benzopyrans such as mono-, di- and trisubstituted benzopyran derivatives and additional ring-fused benzopyrans such as benzopyranoisoxazoles, benzopyranopyrazoles, six-membered ring-fused

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This review covers the construction of drug-like 2H-benzopyrans and related libraries using solid-phase parallel synthesis. In this context, the preparation of substituted benzopyrans such as mono-, di- and trisubstituted benzopyran derivatives and additional ring-fused benzopyrans such as benzopyranoisoxazoles, benzopyranopyrazoles, six-membered ring-fused benzopyrans, and polycyclic benzopyrans are highlighted. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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Open AccessReview Recent Applications of Polymer Supported Organometallic Catalysts in Organic Synthesis

by Nina Kann

Molecules 2010, 15(9), 6306-6331; https://doi.org/10.3390/molecules15096306

Received: 18 June 2010 / Revised: 18 August 2010 / Accepted: 2 September 2010 / Published: 7 September 2010

Cited by 50 | PDF Full-text (227 KB)

Abstract

Recent developments concerning the application of polymer supported organometallic reagents in solid phase synthesis are reviewed, with a special focus on methodology for carbon-carbon formation. Examples of reactions that are covered include the classical Suzuki, Sonogashira and Heck coupings, but also aryl amination,

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Recent developments concerning the application of polymer supported organometallic reagents in solid phase synthesis are reviewed, with a special focus on methodology for carbon-carbon formation. Examples of reactions that are covered include the classical Suzuki, Sonogashira and Heck coupings, but also aryl amination, epoxide opening, rearrangements, metathesis and cyclopropanation. Applications in the field of asymmetric synthesis are also discussed. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

Open AccessReview Solid-Phase Synthesis of N-Substituted Glycine Oligomers (α‑Peptoids) and Derivatives

by Adrian S. Culf and Rodney J. Ouellette

Molecules 2010, 15(8), 5282-5335; https://doi.org/10.3390/molecules15085282

Received: 4 June 2010 / Revised: 14 July 2010 / Accepted: 2 August 2010 / Published: 4 August 2010

Cited by 87 | PDF Full-text (437 KB) | Supplementary Files

Abstract

Peptoids (N-substituted polyglycines and extended peptoids with variant backbone amino-acid monomer units) are oligomeric synthetic polymers that are becoming a valuable molecular tool in the biosciences. Of particular interest are their applications to the exploration of peptoid secondary structures and drug

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Peptoids (N-substituted polyglycines and extended peptoids with variant backbone amino-acid monomer units) are oligomeric synthetic polymers that are becoming a valuable molecular tool in the biosciences. Of particular interest are their applications to the exploration of peptoid secondary structures and drug design. Major advantages of peptoids as research and pharmaceutical tools include the ease and economy of synthesis, highly variable backbone and side-chain chemistry possibilities. At the same time, peptoids have been demonstrated as highly active in biological systems while resistant to proteolytic decay. This review with 227 references considers the solid-phase synthetic aspects of peptoid preparation and utilization up to 2010 from the instigation, by R. N. Zuckermann et al., of peptoid chemistry in 1992. Full article

(This article belongs to the Special Issue Solid Phase Synthesis)

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