Special Issue "Solid Phase Synthesis"

Guest Editor
Prof. Dr. Fernando Albericio
Institute for Research in Biomedicine (IRB Barcelona), Parc Científic de Barcelona, Baldiri Reixac 10, 08028 Barcelona, Spain
Website: http://www.pcb.ub.es/fama
E-Mail:
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
E-Mail:
Interests: depsipeptides; peptide architectures; solid-phase chemistry; protecting groups; amino and hydroxy acids

Submission

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

Type of paper: Article
Title: Solid-Phase Synthesis of Linker Tagged Aryl-Triazine Library via Suzuki Cross-Coupling Reaction
Authors: Young-Tae Chang; James Ha
Affiliation: Department of Chemistry, National University of Singapore, Science Drive 3, Singapore; E-mail: chmcyt@nus.edu.sg (Y.-T. C.) jacs@paran.com (J. H.)
Abstract: To expand the linker tagged tri-substituted triazine libraries to incorporate the Suzuki cross-coupling reaction, we employed an efficient orthogonal synthesis for aryl diversification via Suzuki arylation on solid-support. The mono-substituted triazine building block with triethylene glycol (TG) as the linker were captured by amino acid loaded polystyrene resin, followed by Suzuki arylation and the resulting intermediates achieved linker tagged aryl-triazine library by acidic cleavage reaction with high purity.
Keywords: triethylene glycol (TG) linker, aryl-triazine library, Suzuki cross-coupling reaction

Type of Paper: Review
Title: Solid-Phase Synthesis of N-Substituted Glycines (α-Peptoids) and Derivatives.
Auhtor: Adrian S. Culf ^1,2
Affiliations: ¹ Atlantic Cancer Research Institute, 35 Providence Street, Moncton, NB. EIC 8X3, Canada; E-Mail: adrianc@canceratl.ca
² Dept. of Chemistry and Biochemistry, Mount Allison University, 63C York Street, Sackville, NB. E4L 1G8, Canada; E-Mail: aculf@mta.ca
Abstract: Peptoids (N-substituted polyglycines and extended peptoids with variant backbone amino-acid monomer units) are oligomeric synthetic polymers of interest to the bio-scientific community. The ease and economy of synthesis and highly variable backbone and side-chain chemistry possibilities combined with their demonstrated activity in biological systems and resistance to proteolytic decay has placed peptoids as a valuable molecular tool into several arenas, including the elucidation of peptidic folding parameters to yield secondary structures, protein ligation and drug design. This review will consider the solid-phase synthetic aspects of peptoid preparation and utilization from the instigation, by R. N. Zuckermann, of peptoid chemistry in 1992.

Title: Solid Phase Strategies for Standard and Modified Peptide Nucleic Acids (PNAs)
Authors: Tullia Tedeschi, Stefano Sforza, Roberto Corradini and Rosangela Marchelli
Affiliation: Dipartimento di Chimica Organica ed Industriale, Università di Parma, Via G.P. Usberti 17/A, 43100 Parma, Italy; E-Mail: tullia.tedeschi@unipr.it (T.T.)
Abstract: Almost 20 years ago Nielsen and coworkers presented for the first time Peptide Nucleic Acids (PNAs), a new class of molecules with the binding properties of DNA, but structuraly similar to peptides.
Since then, an always increasing number of pubblications have described different applications of PNAs in many fields, from biochemistry to biomedical science and diagnostics, by simply exploiting the ability of this molecule to bind complementary sequences of nucleic acids by standard Watson-Crick interactions. Since PNA monomer have an amino and a carboxy terminus, the PNA pseudopeptide backbone can be simply assembled by application of solid phase peptide synthesis protocols, with few modifications taking into account the peculiar PNA structure. Moreover, many modified PNAs have also been presented in these years, in some cases requiring suitable modifications to the solid phase synthetic procedures. As a consequence,also investigations concerning new chemical reactions on solid support for the synthesis of new PNA molecules bearing different functionalities also increased. This review explores the development of solid phase chemistries for the synthesis of standard and modified PNA with different chemical features.

Title: Solid Phase Synthesis of the Lipopeptide Myr-HBVpreS/2-78, a Hepatitis B Virus Entry Iinhibitor
Author: Walter Mier
Affiliation: Abt. für Nuklearmedizin, Radiologische Universitätsklinik, Faculty of Medicine, University of Heidelberg, Heidelberg, Germany; E-Mail: Walter.Mier@med.uni-heidelberg.de
Abstract: Chronic HBV infection is the leading cause of liver cirrhosis and HCC. Synthetic peptides derived from the N-terminus of the large HBV envelope 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. Constituting a novel class of anti HBV drugs an efficient synthesis of this peptide is required. Consequently, the solid phase synthesis of the N-terminal 77 amino acids of the viral L-protein was studied in detail. The sequence 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. NMR studies suggest that the peptide belongs to a class of intrinsically unfolded peptides and is therefore not prone to aggregations within the synthesis. Nevertheless, "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. These studies revealed that the efficiency of the synthesis could be increased best by applying elevated temperature resulting in a higher purity of the crude product after solid phase synthesis. These data show that it was possible to minimize the occurrence of side products related to incomplete coupling steps. In conclusion, the peptide is accessible by stepwise SPPS without the necessity of segment coupling.