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.
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 language | English |
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Publication status | Published - 28 Jun 2016 |
Event | Tetrahedron Symposium - Barcelona, Barcelona, Spain Duration: 28 Jun 2016 → 1 Jul 2016 |
Conference
Conference | Tetrahedron Symposium |
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Country/Territory | Spain |
City | Barcelona |
Period | 28/06/16 → 1/07/16 |