“Endogenous human SEC14-like protein nano-constructs” |
Our current research focuses on proteins of the SEC14-like family (1). These proteins are involved in the targeted transfer of specific lipids throughout the human body. In particular, cellular retinal binding protein (CRALBP) promotes persistent vision by facilitating the flow of retinal in the human eye (2).
As a consequence, single missense mutations of the CRALBP gene product RLBP1 are associated with severe retinal pathologies ultimately causing loss of vision (3,4). The structurally related alpha-tocopherol transfer protein (α-TTP) is essential for the retention of vitamin E in man (5), and missense mutations of its gene-product TTPA may cause autosomal recessive ataxia with isolated Vitamin E deficiency (6).
We have shown that α-TTP, as well as CRALBP, may form nano-spherical aggregates when bound to their cognate ligands α-tocopherol and 11-cis-retinal respectively (7,8). We have also demonstrated the modulation of ligand binding in the cavity of α-TTP by site-directed mutagenesis (9).
Our research is aiming to develop non-immunogenic nano-particles for the targeted delivery of otherwise insoluble drugs into human tissues. We are currently testing the hypothesis that nano-spherical aggregates of CRALBP and α-TTP may represent natural carriers for the transport of new pharmacological compounds into the central nervous system and more specifically into the eye (7,8).
[1] Helbling, R.E. et al. J. Phys. Chem. B 2013, 117, 10719; Bolze, C.S. et al., J. Am. Chem. Soc.
2014, 136, 137; Helbling, R.E. et al., CHIMIA 2014, 68, 615; Christen, M. et al., J. Struct. Biol.
2015, 190, 261; Lamprakis, C. et al. Front. Mol. Biosci. 2015, 2, 36.
[2] Burstedt, M.S. et al., Vision Res. 2003, 43:2559–2571.
[3] Maw, M.A., et al., Nat. Genet. 1997, 17:198-200.
[4] Xiaoqin, He. et al., PNAS, 2009, 106:18545–18550.
[5] Kono, N. and Arai, H., Traffic 2015, 16: 19–34.
[6] Ouahchi, K., et al., Nat. Genet. 1995 9:141-145.
[7] Aeschimann, W. et al., Scientific Reports 2017 7: 4970 | DOI:10.1038/s41598-017-05148-9
[8] Europäische Patentanmeldung Nr. EP16152579.5.
[9] RE Helbling, R.E. et al., PLoS ONE 2012, 7, e49195.
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