Synthesis and Biological Evaluation of Two Mannose 6-Phosphate Analogs

Vidal, Sébastien; Vidil, Carole; Morére, Alain; Garcia, Marcel; Montéro, Jean-Louis

doi:10.1002/1099-0690(200010)2000:20<3433::aid-ejoc3433>3.0.co;2-i

Cited by 16 publications

(11 citation statements)

References 16 publications

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“…(3)). On the other hand, thehydroxyphosphonate isosteric analogues 3 can not bind to CI-M6PR [48]. This means that the replacement of the phosphomonoester linkage by a methylene group does not affect the recognition phenomenon [47] but, further substitutions at the 6-position decrease the ligand-receptor interaction, probably by steric hindrance [48].…”

Section: Recognition Requirementsmentioning

confidence: 99%

Mannose 6-Phosphate Receptor Targeting and its Applications in Human Diseases

Gary‐Bobo

Nirdé²,

Jeanjean³

et al. 2007

CMC

154

112

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The cation-independent mannose 6-phosphate receptor is a multifunctional protein which binds at the cell surface to two distinct classes of ligands, the mannose 6-phosphate (M6P) bearing proteins and IGF-II. Its major function is to bind and transport M6P-enzymes to lysosomes, but it can also modulate the activity of a variety of extracellular M6P-glycoproteins (i.e., latent TGFbeta precursor, urokinase-type plasminogen activator receptor, Granzyme B, growth factors, Herpes virus). The purpose of this review is to highlight the synthesis and potential use of high affinity M6P analogues able to target this receptor. Several M6P analogues with phosphonate, carboxylate or malonate groups display a higher affinity and a stronger stability in human serum than M6P itself. These derivatives could be used to favour the delivery of specific therapeutic compounds to lysosomes, notably in enzyme replacement therapies of lysosomal diseases or in neoplastic drug targeting. In addition, their potential applications in preventing clinical disorders, which are associated with the activities of other M6P-proteins involved in wound healing, cell growth or viral infection, will be discussed.

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Section: Recognition Requirementsmentioning

confidence: 99%

Mannose 6-Phosphate Receptor Targeting and its Applications in Human Diseases

Gary‐Bobo

Nirdé²,

Jeanjean³

et al. 2007

CMC

154

112

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“…[56] The subsequent syn-dihydroxylation yielded the (6S,7R)-isomer as expected from the Kishis rule. A similar sequence has been followed in the literature for generating analogues of mannose-6-phosphates.…”

Section: Resultsmentioning

confidence: 68%

“…A similar sequence has been followed in the literature for generating analogues of mannose-6-phosphates. [56] The subsequent syn-dihydroxylation yielded the (6S,7R)-isomer as expected from the Kishis rule. [57] The two configurations were ascertained by X-ray crystallography of peracetate 41 obtained after reduction of the ester.…”

Section: Synthesis Of Octosides and Phosphonates Analogues Ofmentioning

confidence: 68%

Systematic Synthesis of Inhibitors of the Two First Enzymes of the Bacterial Heptose Biosynthetic Pathway: Towards Antivirulence Molecules Targeting Lipopolysaccharide Biosynthesis

Durka

Tikad

Périon

et al. 2011

Chemistry A European J

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L-Heptoses (L-glycero-D-manno-heptopyranoses) are constituents of the inner core of lipolysaccharide (LPS), a molecule playing key roles in the mortality of many infectious diseases as well as in the virulence of many human pathogens. The inhibition of the first enzymes of the bacterial heptose biosynthetic pathway is an almost unexplored field to date although it appears to be a very novel way for the development of antivirulence drugs. We report the synthesis of a series of D-glycero-D-manno-heptopyranose 7-phosphate (H7P) analogues and their inhibition properties against the isomerase GmhA and the the kinase HldE, the two first enzymes of the bacterial heptose biosynthetic pathway. The heptose structures have been modified at the 1-, 2-, 6- and 7-positions to probe the importance of the key structural features of H7P that allow a tight binding to the target enzymes; H7P being the product of GmhA and the substrate of HldE, the second objective was to find structures that could simultaneously inhibit both enzymes. We found that GmhA and HldE were extremely sensitive to structural modifications at the 6- and 7- positions of the heptose scaffold. To our surprise, the epimeric analogue of H7P displaying a D-glucopyranose configuration was found to be the best inhibitor of both enzymes but also the only molecule of this series that could inhibit GmhA (IC(50)=34 μM) and HldE (IC(50)=9.4 μM) in the low micromolar range. Noteworthy, this study describes the first inhibitors of GmhA ever reported, and paves the way to the design of a second generation of molecules targeting the bacterial virulence.

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“…Alternatively, reaction of freshly prepared aldehyde 8 with diethyl phosphite [24] in DCM and triethylamine (TEA) gave α-hydroxyphosphonate 12 in 89 % yield over two steps (Scheme 3). Subsequent cleavage of the benzyl group in EtOH and Pd(OH) 2 (compound 13, quantitative yield), followed by deprotection of the phosphonate ethyl groups with TMSBr and pyridine in acetonitrile gave compound 14 (60 % yield).…”

Section: Chemistrymentioning

confidence: 99%

Phosphonate Analogues of Arabinose 5‐Phosphate: Putative Ligands for Arabinose 5‐Phosphate Isomerases

Gabrielli¹,

Airoldi²,

Sperandeo³

et al. 2013

Eur J Org Chem

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Metabolically stable arabinose 5‐phosphate analogues possessing phosphate mimetic groups at the 5‐position were synthesized and evaluated by saturation‐transfer‐difference (STD) NMR studies for their ability to interact with arabinose 5‐phosphate isomerase. Isosteric methylphosphonate 1 and (difluoromethyl)phosphonate 3 were recognised and bound by the catalytic pocket of the enzyme. The synthesized compounds were tested in vivo on E. coli and P. aeruginosa strains in order to evaluate their antibacterial activity.

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Synthesis and Biological Evaluation of Two Mannose 6-Phosphate Analogs

Cited by 16 publications

References 16 publications

Mannose 6-Phosphate Receptor Targeting and its Applications in Human Diseases

Mannose 6-Phosphate Receptor Targeting and its Applications in Human Diseases

Systematic Synthesis of Inhibitors of the Two First Enzymes of the Bacterial Heptose Biosynthetic Pathway: Towards Antivirulence Molecules Targeting Lipopolysaccharide Biosynthesis

Phosphonate Analogues of Arabinose 5‐Phosphate: Putative Ligands for Arabinose 5‐Phosphate Isomerases

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