| Autor: |
Seebach, Dieter, Widmer, Hans, Capone, Stefania, Ernst, Richard, Bremi, Tobias, Kieltsch, Iris, Togni, Antonio, Monna, Dominique, Langenegger, Daniel, Hoyer, Daniel |
| Zdroj: |
Helvetica Chimica Acta; Dec2009, Vol. 92 Issue 12, p2577-2586, 10p |
| Abstrakt: |
The previously reported ( Helv. Chim. Acta 2008, 91, 2035) derivatives of octreotide ( 1) with a (CF3)-Trp substitution, i.e., 3, and with open-chain structures, i.e., 2, 4, and 5, have been tested for their affinities to hsst1-5 receptors and subjected to a detailed NMR analysis. Their affinities vary from 15 n M to 5 μ M, as compared to 0.6 n M to 0.8 μ M for octreotide itself ( Table 1). This decreased bioactivity may have had to be expected for the open-chain compounds 4 and 5; possible reasons for this decrease in the case of CF3 derivative of octreotide, 3, are discussed. NMR Analysis ( Tables 2 and 3) provides evidence for increased dynamics of all new derivatives 2- 5. The dynamics of the octreotide molecule 1 was analyzed by (natural-abundance) longitudinal 13C-T1-relaxation time measurements ( Table 4), from which the conclusion is drawn that the backbone of the macrocycle is rather rigid on the time scale of this method. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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