Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase
Sufferers of cystic fibrosis are at significant risk of contracting chronic bacterial lung infections. The dominant pathogen in these cases is mucoid Pseudomonas aeruginosa. Such infections are characterised by overproduction of the exopolysaccharide alginate. We present herein the design and chemoe...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Beilstein-Institut
2022-09-01
|
| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.18.142 |
| _version_ | 1811229654180167680 |
|---|---|
| author | Sanaz Ahmadipour Alice J. C. Wahart Jonathan P. Dolan Laura Beswick Chris S. Hawes Robert A. Field Gavin J. Miller |
| author_facet | Sanaz Ahmadipour Alice J. C. Wahart Jonathan P. Dolan Laura Beswick Chris S. Hawes Robert A. Field Gavin J. Miller |
| author_sort | Sanaz Ahmadipour |
| collection | DOAJ |
| description | Sufferers of cystic fibrosis are at significant risk of contracting chronic bacterial lung infections. The dominant pathogen in these cases is mucoid Pseudomonas aeruginosa. Such infections are characterised by overproduction of the exopolysaccharide alginate. We present herein the design and chemoenzymatic synthesis of sugar nucleotide tools to probe a critical enzyme within alginate biosynthesis, GDP-mannose dehydrogenase (GMD). We first synthesise C6-modified glycosyl 1-phosphates, incorporating 6-amino, 6-chloro and 6-sulfhydryl groups, followed by their evaluation as substrates for enzymatic pyrophosphorylative coupling. The development of this methodology enables access to GDP 6-chloro-6-deoxy-ᴅ-mannose and its evaluation against GMD. |
| first_indexed | 2024-04-12T10:18:10Z |
| format | Article |
| id | doaj.art-897c1b0ffb0340a0afbd2a9a48f64934 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-04-12T10:18:10Z |
| publishDate | 2022-09-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-897c1b0ffb0340a0afbd2a9a48f649342022-12-22T03:37:10ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972022-09-011811379138410.3762/bjoc.18.1421860-5397-18-142Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenaseSanaz Ahmadipour0Alice J. C. Wahart1Jonathan P. Dolan2Laura Beswick3Chris S. Hawes4Robert A. Field5Gavin J. Miller6Department of Chemistry & Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK Department of Chemistry & Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK Sufferers of cystic fibrosis are at significant risk of contracting chronic bacterial lung infections. The dominant pathogen in these cases is mucoid Pseudomonas aeruginosa. Such infections are characterised by overproduction of the exopolysaccharide alginate. We present herein the design and chemoenzymatic synthesis of sugar nucleotide tools to probe a critical enzyme within alginate biosynthesis, GDP-mannose dehydrogenase (GMD). We first synthesise C6-modified glycosyl 1-phosphates, incorporating 6-amino, 6-chloro and 6-sulfhydryl groups, followed by their evaluation as substrates for enzymatic pyrophosphorylative coupling. The development of this methodology enables access to GDP 6-chloro-6-deoxy-ᴅ-mannose and its evaluation against GMD.https://doi.org/10.3762/bjoc.18.142alginatechemical probeenzymatic synthesisgdp-mannose dehydrogenasesugar nucleotide |
| spellingShingle | Sanaz Ahmadipour Alice J. C. Wahart Jonathan P. Dolan Laura Beswick Chris S. Hawes Robert A. Field Gavin J. Miller Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase Beilstein Journal of Organic Chemistry alginate chemical probe enzymatic synthesis gdp-mannose dehydrogenase sugar nucleotide |
| title | Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase |
| title_full | Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase |
| title_fullStr | Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase |
| title_full_unstemmed | Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase |
| title_short | Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase |
| title_sort | synthesis of c6 modified mannose 1 phosphates and evaluation of derived sugar nucleotides against gdp mannose dehydrogenase |
| topic | alginate chemical probe enzymatic synthesis gdp-mannose dehydrogenase sugar nucleotide |
| url | https://doi.org/10.3762/bjoc.18.142 |
| work_keys_str_mv | AT sanazahmadipour synthesisofc6modifiedmannose1phosphatesandevaluationofderivedsugarnucleotidesagainstgdpmannosedehydrogenase AT alicejcwahart synthesisofc6modifiedmannose1phosphatesandevaluationofderivedsugarnucleotidesagainstgdpmannosedehydrogenase AT jonathanpdolan synthesisofc6modifiedmannose1phosphatesandevaluationofderivedsugarnucleotidesagainstgdpmannosedehydrogenase AT laurabeswick synthesisofc6modifiedmannose1phosphatesandevaluationofderivedsugarnucleotidesagainstgdpmannosedehydrogenase AT chrisshawes synthesisofc6modifiedmannose1phosphatesandevaluationofderivedsugarnucleotidesagainstgdpmannosedehydrogenase AT robertafield synthesisofc6modifiedmannose1phosphatesandevaluationofderivedsugarnucleotidesagainstgdpmannosedehydrogenase AT gavinjmiller synthesisofc6modifiedmannose1phosphatesandevaluationofderivedsugarnucleotidesagainstgdpmannosedehydrogenase |