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- Title
Distamycin-NA: A DNA analog with an aromatic heterocyclic polyamide backbone. Part 2. Solid-phase synthesis of distamycin-NAs containing the nucleobase uracil: Unexpected solvent participation in the coupling step.
- Authors
Sauter, Guido; Leumann, Christian
- Abstract
The synthesis of the Fmoc-protected amino acid 2 is presented. First attempts of amide-bond formation to the homodimer 4 in solution showed only poor coupling yields indicative for the low reactivity of the amino and carboxy groups in the building blocks 1 and 2, respectively ( Scheme 1). Best coupling yields were found using dicyclohexylcarbodiimide (DCC) without any additive. The oligomerization of building block 2 adopting the Fmoc ((9 H-fluoren-9-ylmethoxy)carbonyl) solid-phase synthesis yielded a mixture of N-terminal-modified distamycin-NA derivatives. By combined HPLC and MALDI-TOF-MS analysis, the N-terminal functional groups could be identified as acetamide and N, N-dimethylformamidine functions, arising from coupling of the N-terminus of the growing chain with residual AcOH or DCC-activated solvent DMF. An improved preparation of building block 2 and coupling protocol led to the prevention of the N-terminal acetylation. However, 'amidination' could not be circumvented. A thus isolated tetramer of 2, containing a lysine unit at the C-terminus and a N, N-dimethylformamidine-modified N-terminus, not unexpectedly, showed no complementary base pairing to DNA and RNA, as determined by standard UV-melting-curve analysis.
- Publication
Helvetica Chimica Acta, 1998, Vol 81, Issue 5-8, p916
- ISSN
0018-019X
- Publication type
Article
- DOI
10.1002/hlca.19980810512