Synthesis of C-11 linked active ester derivatives of vitamin D3 and their conjugations to 42-residue helix-loop-helix peptides |
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Authors: | Qi Zhang Thomas Norberg Jonas Bergquist |
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Affiliation: | a Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, SE-751 23 Uppsala, Sweden b Department of Physical and Analytical Chemistry, Uppsala University, Box 579, 75123 Uppsala, Sweden |
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Abstract: | Derivatives of vitamin D3 carrying an 8-carbon linker at C-11 terminating in an active ester were synthesized from commercial vitamin D3 using a disassembly-reassembly strategy. Vitamin D3 was cleaved at the C6-C7 double bond and the ‘upper’ fragment was converted, via a series of reactions, to derivatives substituted at C-11 with an 8-carbon linker terminating in an ethyl ester. Reassembly with modified ‘lower’ fragments using Horner-Wittig olefination followed by linker ester hydrolysis and re-esterification with p-nitrophenol gave C-11 substituted p-nitrophenyl esters. These vitamin D derivatives were conjugated to 42-amino acid helix-loop-helix peptides by reaction of their p-nitrophenyl esters with lysyl side-chain amino groups on the peptides. The vitamin D—peptide conjugates, being potential specific binder candidates for vitamin D-binding protein, were characterized by mass spectroscopy and CD measurements. |
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Keywords: | YTEZMYOZYFTBON-HXGKWGOXSA-N YTEZMYOZYFTBON-HXGKWGOXSA-N NFJZSYYDPDBWSX-LVPBUHHKSA-N |
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