Synthesis of a Tethered myo-Inositol (1,3,4,5,6)Pentakisphosphate (IP5) Derivative as a Probe for Biological Studies

Mark Gregory; Bruno Catimel; Meng-Xin Yin; Melanie Condron; Antony W. Burgess; Andrew B. Holmes

doi:10.1055/s-0035-1560381

Synlett, Table of Contents

Synlett 2016; 27(01): 121-125
DOI: 10.1055/s-0035-1560381

letter

Synthesis of a Tethered myo-Inositol (1,3,4,5,6)Pentakisphosphate (IP5) Derivative as a Probe for Biological Studies

Mark Gregory*

^aSchool of Chemistry, Bio21 Institute, The University of Melbourne, 30 Flemington Road, Parkville, Victoria 3052, Australia Email: m.gregory4@pgrad.unimelb.edu.au Email: aholmes@unimelb.edu.au

,

Bruno Catimel

^bWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia

,

Meng-Xin Yin

^aSchool of Chemistry, Bio21 Institute, The University of Melbourne, 30 Flemington Road, Parkville, Victoria 3052, Australia Email: m.gregory4@pgrad.unimelb.edu.au Email: aholmes@unimelb.edu.au

,

Melanie Condron

^bWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia

,

Antony W. Burgess

^bWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia

,

Andrew B. Holmes*

^aSchool of Chemistry, Bio21 Institute, The University of Melbourne, 30 Flemington Road, Parkville, Victoria 3052, Australia Email: m.gregory4@pgrad.unimelb.edu.au Email: aholmes@unimelb.edu.au

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Abstract

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This paper is dedicated to Prof. Steven Ley on the occasion of his 70^th birthday and in recognition of his pioneering synthesis of the GPI anchor.

Abstract

There is sufficient evidence to suggest that myo-inositol pentakisphosphate is a vital intermediate species in higher inositol phosphate metabolism, however, its biological roles and physiological function in cells remain uncertain. A tethered myo-inositol pentakisphosphate (IP5) derivative with a terminal amine group is synthesised allowing facilitated immobilisation onto M-270 magnetic Dynabeads for pull-down experiments and biosensor chip preparation for surface plasmon resonance studies. The probes are validated by both pull-down and surface plasmon resonance (SPR) studies of the known binding protein GRP-1 (general receptor for phosphoinositides 1), and furthermore by SPR studies of protein kinase B (PKB or AKT) binding.

Key words

protecting groups - proteins - total synthesis - regioselectivity - carbohydrates - phosphates - bioorganic chemistry - hydrogenation

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References

References and Notes
1 Potter BV. L, Lampe D. Angew. Chem., Int. Ed. Engl. 1995; 34: 1933
2 Prestwich G. Chem. Biol. 2004; 11: 619
3 Berridge M, Irvine R. Nature 1984; 312: 315
4 Best M, Zhang H, Prestwich G. Nat. Prod. Rep. 2010; 27: 1403
5 Johnson LF, Tate ME. Ann. N. Y. Acad. Sci. 1970; 165: 526

6a Irvine R, Schell M. Nat. Rev. Mol. Cell Biol. 2001; 2: 327
6b French P, Bunce C, Stephens L, Lord J, McConnell F, Brown G, Creba J, Michell R. Proc. R. Soc. London, Ser. B 1991; 245: 193

7 Menniti F, Miller R, Putney J, Shears S. J. Biol. Chem. 1993; 268: 3850
8 Steger DJ, Haswell ES, Miller AL, Wente SR, O’Shea EK. Science 2003; 299: 114
9 Quignard JF, Rakotoarisoa L, Mironneau J, Mironneau C. J. Physiol. 2003; 549: 729
10 Piccolo E, Vignati S, Maffucci T, Innominato P, Riley A, Potter B, Pandolfi P, Broggini M, Iacobelli S, Innocenti P, Falasca M. Oncogene 2004; 23: 1754
11 Campbell S, Fisher RJ, Towler EM, Fox S, Issaq HJ, Wolfe T, Phillips LR, Rein A. Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 10875
12 Gao Y, Wang H.-y. J. Biol. Chem. 2007; 282: 26490
13 Rzepecki P, Prestwich G. J. Org. Chem. 2002; 67: 5454
14 Rossi A, Riley A, Tovey S, Rahman T, Dellis O, Taylor E, Veresov V, Potter B, Taylor C. Nat. Chem. Biol. 2009; 5: 631
15 Conway S, Gardiner J, Grove S, Johns M, Lim Z.-Y, Painter G, Robinson DE. J, Schieber C, Thuring J, Wong L, Yin M.-X, Burgess A, Catimel B, Hawkins P, Ktistakis N, Stephens L, Holmes AB. Org. Biomol. Chem. 2010; 8: 66

16a Catimel B, Schieber C, Condron M, Patsiouras H, Connolly L, Catimel J, Nice EC, Burgess AW, Holmes AB. J. Proteome Res. 2008; 7: 5295
16b Catimel B, Yin M.-X, Schieber C, Condron M, Patsiouras H, Catimel J, Robinson DE. J. E, Wong LS.-M, Nice EC, Holmes AB, Burgess AW. J. Proteome Res. 2009; 8: 3712
16c Catimel B, Kapp E, Yin M.-X, Gregory M, Wong LS.-M, Condron M, Church N, Kershaw N, Holmes AB, Burgess AW. J. Proteomics 2013; 82: 35

17 Prestwich GD, Marecek JF, Mourey RJ, Theibert AB, Ferris CD, Danoff SK, Snyder SH. J. Am. Chem. Soc. 1991; 113: 1822
18 Ozaki S, Koga Y, Ling L, Watanabe Y, Kimura Y, Hirata M. Bull. Chem. Soc. Jpn. 1994; 67: 1058

19a Billington DC, Baker R, Kulagowski JJ, Mawer IM, Vacca JP, Desolms SJ, Huff JR. J. Chem. Soc., Perkin Trans. 1 1989; 1423
19b Lee HW, Kishi Y. J. Org. Chem. 1985; 50: 4402

20 Lampe D, Liu C, Potter BV. L. J. Med. Chem. 1994; 37: 907

21a Lim Z.-Y, Thuring JW, Holmes AB, Manifava M, Ktistakis NT. J. Chem. Soc., Perkin Trans. 1 2002; 1067
21b Gilbert IH, Holmes AB, Young RC. Tetrahedron Lett. 1990; 31: 2633
21c Gilbert IH, Holmes AH, Pestchanker MJ, Young RC. Carbohydr. Res. 1992; 234: 117

22a Ogawa T, Nakabayashi S. Carbohydr. Res. 1981; 93: C1
22b Keddie NS, Ye Y, Aslam T, Luyten T, Bello D, Garnham C, Bulynck G, Galione A, Conway SJ. Chem. Commun. 2011; 47: 242

23 Corson T, Aberle N, Crews C. ACS Chem. Biol. 2008; 3: 677
24 Zhang H, Thompson J, Prestwich G. Org. Lett. 2009; 11: 1551
25 5-O-Amino Ethoxyethyl-phosphate-myo-inositol-1,3,4,6-tetraphosphate (1) To a solution of the fully protected derivative 16 (10 mg, 72 μmol) dissolved in MeOH–THF (2:3, 2 mL) was added Pd(OH)₂ (10 mg). The mixture was reacted under H₂ (10 bar pressure, in a Buchi hydrogenation vessel) and was allowed to stir vigorously at r.t. for 48 h. The mixture was filtered twice through Celite and the filtrate was lyophilised to give the desired product 1 (5 mg, quant.) as a white powder. IR (neat): 3500–3000 (br), 1579, 1409, 1353, 1087, 973 cm^-1. ¹H NMR (500 MHz, D₂O): δ = 4.60–4.40 (m, 5 H), 4.25 (br s, 1 H), 4.14 (br s, 2 H), 3.88–3.81 (m, 4 H), 3.76–3.64 (m, 2 H), 3.14 (br s, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 76.7, 76.2, 75.5, 73.0, 71.6, 69.9, 66.3, 66.0, 60.4, 39.2. ³¹P NMR (202 MHz, CDCl₃): δ = 4.22 (2 P), 3.01 (2 P), 0.44 (1 P). HRMS (ESI): m/z [M – H]^– calcd for C₁₀H₂₅NO₂₂P₅: 665.9562; found: 665.9587; m/z [M – 2 H]^2– calcd for C₁₀H₂₄NO₂₂P₅: 332.4745; found: 332.4755.
26 Jackson SG, Al-Saigh S, Schultz C, Junop M. BMC Struct. Biol. 2011; 11: 11
27 Nguyen T, Goodrich J. Nat. Methods 2006; 3: 135
28 Kavran J, Klein D, Lee A, Falasca M, Isakoff S, Skolnik E, Lemmon M. J. Biol. Chem. 1998; 273: 30497

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