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Special Issue "Bioorthogonal Chemistry"

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A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 November 2013)

Special Issue Editor

Guest Editor
Dr. Floris van Delft

Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, NL-6525 AJ Nijmegen, The Netherlands
Website | E-Mail
Interests: bioconjugation; copper-free click chemistry; glycopeptides; nucleotide conjugates; oligosaccharide synthesis; small molecule synthesis; catalysis; chemical biology

Special Issue Information

Dear Colleagues.

The recent strategy to apply chemical reactions to address fundamental biological questions has led to the emergence of entirely new conjugation reactions that are fast and irreversible, yet so mild and selective that they can be performed even in or on living cells or in whole organisms. These so-called bioorthogonal reactions, for example the strain-promoted cycloaddition of cyclooctyne with azide or tetrazine, or trans-cyclooctene with tetrazine, open novel avenues, not only in chemical biology research, but also in many other life sciences applications, including the site-specific modification of proteins, in vitro diagnostics, biomaterials, regenerative medicine, imaging and potentially even image-guided surgery. Research papers and reviews dealing with the presented fields are welcome for the preparation of this Special Issue of Molecules.

Dr. Floris van Delft
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).


Keywords

  • bioorthogonal reactions
  • copper-free click
  • strain-promoted cycloaddition
  • in vivo chemistry
  • biomaterial science
  • peptidoglycans
  • glycoproteins
  • nucleotide conjugates
  • site-specific conjugation
  • immobilization

Published Papers (4 papers)

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Research

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Open AccessArticle Pharmacophore Generation from a Drug-like Core Molecule Surrounded by a Library Peptide via the 10BASEd-T on Bacteriophage T7
Molecules 2014, 19(2), 2481-2496; doi:10.3390/molecules19022481
Received: 30 December 2013 / Revised: 10 February 2014 / Accepted: 12 February 2014 / Published: 21 February 2014
Cited by 3 | PDF Full-text (1983 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASEd-T) undergoes almost quantitatively like a click reaction without side reaction or loss
[...] Read more.
We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASEd-T) undergoes almost quantitatively like a click reaction without side reaction or loss of phage infectivity. The post-translational modification yield, as well as the site-specificity, is quantitatively analyzed by a fluorescent densitometric analysis after gel electrophoresis. The detailed structure of the modified peptide on phage is identified with tandem mass spectrometry. Construction of such a peptide-fused phage library possessing non-natural core structures will be useful for future drug discovery. For this aim, we propose a novel concept of pharmacophore generation from a drug-like molecule (i.e., salicylic acid) conjugated with surrounding randomized peptides. By using the hybrid library, streptavidin-specific binders are isolated through four rounds of biopanning. Full article
(This article belongs to the Special Issue Bioorthogonal Chemistry)
Figures

Open AccessArticle Coupling Bioorthogonal Chemistries with Artificial Metabolism: Intracellular Biosynthesis of Azidohomoalanine and Its Incorporation into Recombinant Proteins
Molecules 2014, 19(1), 1004-1022; doi:10.3390/molecules19011004
Received: 4 December 2013 / Revised: 7 January 2014 / Accepted: 9 January 2014 / Published: 15 January 2014
Cited by 11 | PDF Full-text (735 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this paper, we present a novel, “single experiment” methodology based on genetic engineering of metabolic pathways for direct intracellular production of non-canonical amino acids from simple precursors, coupled with expanded genetic code. In particular, we engineered the intracellular biosynthesis of L-azidohomoalanine from
[...] Read more.
In this paper, we present a novel, “single experiment” methodology based on genetic engineering of metabolic pathways for direct intracellular production of non-canonical amino acids from simple precursors, coupled with expanded genetic code. In particular, we engineered the intracellular biosynthesis of L-azidohomoalanine from O-acetyl-L-homoserine and NaN3, and achieved its direct incorporation into recombinant target proteins by AUG codon reassignment in a methionine-auxotroph E. coli strain. In our system, the host’s methionine biosynthetic pathway was first diverted towards the production of the desired non-canonical amino acid by exploiting the broad reaction specificity of recombinant pyridoxal phosphate-dependent O-acetylhomoserine sulfhydrylase from Corynebacterium glutamicum. Then, the expression of the target protein barstar, accompanied with efficient L-azidohomoalanine incorporation in place of L-methionine, was accomplished. This work stands as proof-of-principle and paves the way for additional work towards intracellular production and site-specific incorporation of biotechnologically relevant non-canonical amino acids directly from common fermentable sources. Full article
(This article belongs to the Special Issue Bioorthogonal Chemistry)
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Review

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Open AccessReview Applications of Copper-Catalyzed Click Chemistry in Activity-Based Protein Profiling
Molecules 2014, 19(2), 1378-1393; doi:10.3390/molecules19021378
Received: 23 December 2013 / Revised: 9 January 2014 / Accepted: 17 January 2014 / Published: 27 January 2014
Cited by 17 | PDF Full-text (390 KB) | HTML Full-text | XML Full-text
Abstract
Activity-based protein profiling (ABPP) is a chemical proteomic technique that enables the interrogation of protein activity directly within complex proteomes. Given the dominant role of posttranslational modifications in regulating protein function in vivo, ABPP provides a direct readout of activity that is
[...] Read more.
Activity-based protein profiling (ABPP) is a chemical proteomic technique that enables the interrogation of protein activity directly within complex proteomes. Given the dominant role of posttranslational modifications in regulating protein function in vivo, ABPP provides a direct readout of activity that is not attained through traditional proteomic methods. ABPP relies on the design of covalent binding probes that either target a specific enzyme or a class of enzymes with related function. These covalent warheads are coupled to either fluorophores or biotin groups for visualization and enrichment of these active proteins. The advent of bioorthogonal chemistries, in particular, the copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC), has benefitted the field of ABPP by achieving the following: (1) replacing bulky reporter groups with smaller alkyne or azide groups to promote cell permeability; (2) adding modularity to the system such that a single probe can be diversified with a variety of reporter groups without the need to develop new synthetic routes; and (3) enabling the conjugation of complex linkers to facilitate quantitative proteomic analyses. Here, we summarize recent examples of CuAAC in ABPP that serve to illustrate the contribution of bioorthogonal chemistry to advancing discoveries in this field. Full article
(This article belongs to the Special Issue Bioorthogonal Chemistry)
Open AccessReview Ring Expansion of Vinylaziridines through the Strain-Release Pericyclic Reaction: Recent Developments and Applications
Molecules 2013, 18(8), 9650-9662; doi:10.3390/molecules18089650
Received: 23 July 2013 / Revised: 1 August 2013 / Accepted: 7 August 2013 / Published: 12 August 2013
Cited by 4 | PDF Full-text (612 KB) | HTML Full-text | XML Full-text
Abstract Recent syntheses of azetidines, pyrrolidines, piperidines and azepines through cycloaddition or sigmatropic rearrangements of vinylaziridines are described. Applications to natural product synthesis and mechanistic investigations are also summarized. Full article
(This article belongs to the Special Issue Bioorthogonal Chemistry)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Review
Title: Chemical Reporters for the Study of Posttranslational Modifica-tions Catalyzed by Native Enzymes
Authors: Ian R. Bothwell 1,2 and Minkui Luo 1,*
Affiliations: 1 Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States; E-Mail: bothweli@mskcc.org
2 Tri-Institutional Training Program in Chemical Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States; E-Mails: luom@mskcc.org; bothweli@mskcc.org
Abstract: Posttranslational modification of proteins involves the addition or removal of chemical functionalities, which elicits changes in their structure and function. Although these modifications are thought to be a significant source of the biochemical diversity observed in living organisms, their broad study has proven difficult using traditional biochemical techniques. In light of this, much recent advancement in the field of posttranslational modi-fications has relied on the development of bioorthogonal chemistry-based approaches, which utilize the distinct specificity of several chemical reactions to covalently label suita-bly reactive surrogate modifications in complex biological milieu for further study. In this review, we will highlight recent works aimed at the study of several posttranslational mod-ifications using this approach for proteomics or biochemical analysis.

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