A Modular Synthesis of an Amphiphilic Oligoaryl-based ApoA1 Mimetic as a Potential Drug Carrier

Patrick Simon Dobrounig, Rolf Breinbauer

Research output: Contribution to conferencePosterResearchpeer-review

Abstract

Apolipoprotein A1 (apoA1), the largest protein of the high density lipoprotein (HDL), has attracted interest for targeted drug delivery.1 Inspired by the structural elements of already existing peptide-based apoA1 mimetics and apoA1 itself, we have designed potential apoA1 mimetics based on an oligoaryl scaffold.2,3 To allow a flexible and modular synthesis of apoA1 mimetics, building blocks were synthesized with a benzene core unit featuring two leaving groups in 1,4-arrangement differing in their reactivity to allow chemoselective borylation and subsequent oligomerization via iterative Pd-catalyzed cross coupling.4 These building blocks are equipped with side chains mimicking on one side the corresponding polar amino acid (Lys, Glu) and on the other side the lipophillic phenylalanine. With this building blocks in hand amphiphillic oligoaryls with an overall low net charge can be synthesized, which will be subsequently tested towards their ability of selectively transporting HDL incorporated small interfering RNA (siRNA) to Scavenger Receptor B1 expressing cells.

References
1. M. M. K. Shahzad, L. S. Mangala, H.H. Han, C. Lu, J. Bottsford-Miller, M. Nishimura, E. M. Mora, J.-W. Lee, R. L. Stone, C. V. Pecot, D. Thanapprapasr, J.-W. Roh, P. Gaur, M. P. Nair, Y.-Y. Park, N. Sabnis, M. T. Deavers, J.-S. Lee, L. M. Ellis, G. Lopez-Berestein, W. J. McConathy, L. Prokai, A. G. Lacko, A. K. Sood, Neoplasia 2011, 13, 309-319.
2. M. Navab, G.M. Anantharamaiah, S. T. Reddy, S. Hama, G. Hough, V. R. Grijalva, N. Yu, B. J. Ansell, G. Datta, D. W. Garber, A. M. Fogelman, Arterioscler. Thromb. Vasc. Biol. 2005, 25, 1325-1331.
3. P. Natarajan, T. M. Forte, B. Chu, M. C. Phillips, J. F. Oram, J. K. Bielicki, J. Biol. Chem. 2004, 279, 24044-24052.
4. E. P. Gillis, M. D. Burke, J. Am. Chem. Soc. 2007, 129, 6716-6717.
Original languageEnglish
Publication statusPublished - 28 Jun 2016
EventTetrahedron Symposium - Barcelona, Barcelona, Spain
Duration: 28 Jun 20161 Jul 2016

Conference

ConferenceTetrahedron Symposium
CountrySpain
CityBarcelona
Period28/06/161/07/16

Cite this

Dobrounig, P. S., & Breinbauer, R. (2016). A Modular Synthesis of an Amphiphilic Oligoaryl-based ApoA1 Mimetic as a Potential Drug Carrier. Poster session presented at Tetrahedron Symposium, Barcelona, Spain.

A Modular Synthesis of an Amphiphilic Oligoaryl-based ApoA1 Mimetic as a Potential Drug Carrier. / Dobrounig, Patrick Simon; Breinbauer, Rolf.

2016. Poster session presented at Tetrahedron Symposium, Barcelona, Spain.

Research output: Contribution to conferencePosterResearchpeer-review

Dobrounig, PS & Breinbauer, R 2016, 'A Modular Synthesis of an Amphiphilic Oligoaryl-based ApoA1 Mimetic as a Potential Drug Carrier' Tetrahedron Symposium, Barcelona, Spain, 28/06/16 - 1/07/16, .
Dobrounig PS, Breinbauer R. A Modular Synthesis of an Amphiphilic Oligoaryl-based ApoA1 Mimetic as a Potential Drug Carrier. 2016. Poster session presented at Tetrahedron Symposium, Barcelona, Spain.
Dobrounig, Patrick Simon ; Breinbauer, Rolf. / A Modular Synthesis of an Amphiphilic Oligoaryl-based ApoA1 Mimetic as a Potential Drug Carrier. Poster session presented at Tetrahedron Symposium, Barcelona, Spain.
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abstract = "Apolipoprotein A1 (apoA1), the largest protein of the high density lipoprotein (HDL), has attracted interest for targeted drug delivery.1 Inspired by the structural elements of already existing peptide-based apoA1 mimetics and apoA1 itself, we have designed potential apoA1 mimetics based on an oligoaryl scaffold.2,3 To allow a flexible and modular synthesis of apoA1 mimetics, building blocks were synthesized with a benzene core unit featuring two leaving groups in 1,4-arrangement differing in their reactivity to allow chemoselective borylation and subsequent oligomerization via iterative Pd-catalyzed cross coupling.4 These building blocks are equipped with side chains mimicking on one side the corresponding polar amino acid (Lys, Glu) and on the other side the lipophillic phenylalanine. With this building blocks in hand amphiphillic oligoaryls with an overall low net charge can be synthesized, which will be subsequently tested towards their ability of selectively transporting HDL incorporated small interfering RNA (siRNA) to Scavenger Receptor B1 expressing cells.References1. M. M. K. Shahzad, L. S. Mangala, H.H. Han, C. Lu, J. Bottsford-Miller, M. Nishimura, E. M. Mora, J.-W. Lee, R. L. Stone, C. V. Pecot, D. Thanapprapasr, J.-W. Roh, P. Gaur, M. P. Nair, Y.-Y. Park, N. Sabnis, M. T. Deavers, J.-S. Lee, L. M. Ellis, G. Lopez-Berestein, W. J. McConathy, L. Prokai, A. G. Lacko, A. K. Sood, Neoplasia 2011, 13, 309-319.2. M. Navab, G.M. Anantharamaiah, S. T. Reddy, S. Hama, G. Hough, V. R. Grijalva, N. Yu, B. J. Ansell, G. Datta, D. W. Garber, A. M. Fogelman, Arterioscler. Thromb. Vasc. Biol. 2005, 25, 1325-1331. 3. P. Natarajan, T. M. Forte, B. Chu, M. C. Phillips, J. F. Oram, J. K. Bielicki, J. Biol. Chem. 2004, 279, 24044-24052.4. E. P. Gillis, M. D. Burke, J. Am. Chem. Soc. 2007, 129, 6716-6717.",
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N2 - Apolipoprotein A1 (apoA1), the largest protein of the high density lipoprotein (HDL), has attracted interest for targeted drug delivery.1 Inspired by the structural elements of already existing peptide-based apoA1 mimetics and apoA1 itself, we have designed potential apoA1 mimetics based on an oligoaryl scaffold.2,3 To allow a flexible and modular synthesis of apoA1 mimetics, building blocks were synthesized with a benzene core unit featuring two leaving groups in 1,4-arrangement differing in their reactivity to allow chemoselective borylation and subsequent oligomerization via iterative Pd-catalyzed cross coupling.4 These building blocks are equipped with side chains mimicking on one side the corresponding polar amino acid (Lys, Glu) and on the other side the lipophillic phenylalanine. With this building blocks in hand amphiphillic oligoaryls with an overall low net charge can be synthesized, which will be subsequently tested towards their ability of selectively transporting HDL incorporated small interfering RNA (siRNA) to Scavenger Receptor B1 expressing cells.References1. M. M. K. Shahzad, L. S. Mangala, H.H. Han, C. Lu, J. Bottsford-Miller, M. Nishimura, E. M. Mora, J.-W. Lee, R. L. Stone, C. V. Pecot, D. Thanapprapasr, J.-W. Roh, P. Gaur, M. P. Nair, Y.-Y. Park, N. Sabnis, M. T. Deavers, J.-S. Lee, L. M. Ellis, G. Lopez-Berestein, W. J. McConathy, L. Prokai, A. G. Lacko, A. K. Sood, Neoplasia 2011, 13, 309-319.2. M. Navab, G.M. Anantharamaiah, S. T. Reddy, S. Hama, G. Hough, V. R. Grijalva, N. Yu, B. J. Ansell, G. Datta, D. W. Garber, A. M. Fogelman, Arterioscler. Thromb. Vasc. Biol. 2005, 25, 1325-1331. 3. P. Natarajan, T. M. Forte, B. Chu, M. C. Phillips, J. F. Oram, J. K. Bielicki, J. Biol. Chem. 2004, 279, 24044-24052.4. E. P. Gillis, M. D. Burke, J. Am. Chem. Soc. 2007, 129, 6716-6717.

AB - Apolipoprotein A1 (apoA1), the largest protein of the high density lipoprotein (HDL), has attracted interest for targeted drug delivery.1 Inspired by the structural elements of already existing peptide-based apoA1 mimetics and apoA1 itself, we have designed potential apoA1 mimetics based on an oligoaryl scaffold.2,3 To allow a flexible and modular synthesis of apoA1 mimetics, building blocks were synthesized with a benzene core unit featuring two leaving groups in 1,4-arrangement differing in their reactivity to allow chemoselective borylation and subsequent oligomerization via iterative Pd-catalyzed cross coupling.4 These building blocks are equipped with side chains mimicking on one side the corresponding polar amino acid (Lys, Glu) and on the other side the lipophillic phenylalanine. With this building blocks in hand amphiphillic oligoaryls with an overall low net charge can be synthesized, which will be subsequently tested towards their ability of selectively transporting HDL incorporated small interfering RNA (siRNA) to Scavenger Receptor B1 expressing cells.References1. M. M. K. Shahzad, L. S. Mangala, H.H. Han, C. Lu, J. Bottsford-Miller, M. Nishimura, E. M. Mora, J.-W. Lee, R. L. Stone, C. V. Pecot, D. Thanapprapasr, J.-W. Roh, P. Gaur, M. P. Nair, Y.-Y. Park, N. Sabnis, M. T. Deavers, J.-S. Lee, L. M. Ellis, G. Lopez-Berestein, W. J. McConathy, L. Prokai, A. G. Lacko, A. K. Sood, Neoplasia 2011, 13, 309-319.2. M. Navab, G.M. Anantharamaiah, S. T. Reddy, S. Hama, G. Hough, V. R. Grijalva, N. Yu, B. J. Ansell, G. Datta, D. W. Garber, A. M. Fogelman, Arterioscler. Thromb. Vasc. Biol. 2005, 25, 1325-1331. 3. P. Natarajan, T. M. Forte, B. Chu, M. C. Phillips, J. F. Oram, J. K. Bielicki, J. Biol. Chem. 2004, 279, 24044-24052.4. E. P. Gillis, M. D. Burke, J. Am. Chem. Soc. 2007, 129, 6716-6717.

M3 - Poster

ER -