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Special Issue "Solid Phase Synthesis"

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Organic Synthesis".

Deadline for manuscript submissions: closed (31 May 2010)

Special Issue Editors

Guest Editor
Prof. Dr. Fernando Albericio

1. School of Chemistry, University of KwaZulu-Natal, Durban 4001, South Africa
2. Department of Organic Chemistry, University of Barcelona, 08028-Barcelona, Spain
Website | E-Mail
Fax: +34 93 403 71 26
Interests: marine natural products; bioactive natural products; peptides; solid-phase chemistry; combinatorial chemistry; drug delivery systems
Guest Editor
Dr. Jan Spengler

Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona, E-08028 Barcelona, Spain
Website | E-Mail
Phone: ++34 934037127
Interests: solid-phase chemistry; protecting groups; backbone modified peptides; depsipeptides; synthesis of rare and non-natural peptide building blocks

Special Issue Information

Dear Colleagues,

Performing reactions in solid phase can speed up considerably the process of the preparation of organic compounds and libraries of their analogs, which is of special importance in drug discovery. However, the reactions usually require conditions different to those used in solution phase chemistry, and also specialized chemical tools. The objective of this issue will be to provide an overview on current investigation in the field of solid-phase synthesis, like the development and evaluation of new polymeric supports, linker, reagents, and also, the scope of chemical reactions in solid phase.

Prof. Dr. Fernando Albericio
Dr. Jan Spengler
Guest Editors

Keywords

  • solid phase organic synthesis
  • solid phase peptide synthesis
  • polymeric supports
  • linker
  • immobilized reagents
  • microwave reactions
  • combinatorial chemistry

Published Papers (11 papers)

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Research

Jump to: Review

Open AccessArticle Development of Designed Site-Directed Pseudopeptide-Peptido-Mimetic Immunogens as Novel Minimal Subunit-Vaccine Candidates for Malaria
Molecules 2010, 15(12), 8856-8889; doi:10.3390/molecules15128856
Received: 26 September 2010 / Accepted: 28 October 2010 / Published: 6 December 2010
Cited by 3 | 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
[...] Read more.
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)
Molecules 2010, 15(9), 6399-6410; doi: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
[...] Read more.
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 TN 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
Molecules 2010, 15(8), 5692-5707; doi:10.3390/molecules15085692
Received: 28 May 2010 / Revised: 28 July 2010 / Accepted: 5 August 2010 / Published: 18 August 2010
Cited by 5 | 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
[...] Read more.
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
Molecules 2010, 15(7), 4961-4983; doi: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
[...] Read more.
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
Molecules 2010, 15(7), 4924-4933; doi: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
Molecules 2010, 15(7), 4773-4783; doi:10.3390/molecules15074773
Received: 20 May 2010 / Revised: 2 July 2010 / Accepted: 5 July 2010 / Published: 7 July 2010
Cited by 8 | 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,
[...] Read more.
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
Molecules 2010, 15(4), 2845-2856; doi:10.3390/molecules15042845
Received: 22 January 2010 / Revised: 15 April 2010 / Accepted: 19 April 2010 / Published: 20 April 2010
Cited by 43 | 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)
[...] Read more.
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
Molecules 2009, 14(10), 3914-3921; doi:10.3390/molecules14103914
Received: 8 September 2009 / Revised: 29 September 2009 / Accepted: 30 September 2009 / Published: 30 September 2009
Cited by 7 | 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
[...] Read more.
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

Jump to: Research

Open AccessReview Solid-Phase Parallel Synthesis of Drug-Like Artificial 2H-Benzopyran Libraries
Molecules 2012, 17(5), 5467-5496; doi:10.3390/molecules17055467
Received: 10 April 2012 / Revised: 25 April 2012 / Accepted: 7 May 2012 / Published: 9 May 2012
Cited by 16 | PDF Full-text (433 KB)
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
[...] Read more.
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
Molecules 2010, 15(9), 6306-6331; doi:10.3390/molecules15096306
Received: 18 June 2010 / Revised: 18 August 2010 / Accepted: 2 September 2010 / Published: 7 September 2010
Cited by 38 | 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,
[...] Read more.
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
Molecules 2010, 15(8), 5282-5335; doi:10.3390/molecules15085282
Received: 4 June 2010 / Revised: 14 July 2010 / Accepted: 2 August 2010 / Published: 4 August 2010
Cited by 68 | 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
[...] Read more.
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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