- Tytuł:
- Cyclic dermorphin tetrapeptide analogues obtained via ring-closing metathesis
- Autorzy:
-
Berezowska, Irena
Chung, Nga
Lemieux, Carole
Wilkes, Brian
Schiller, Peter - Powiązania:
- https://bibliotekanauki.pl/articles/1041269.pdf
- Data publikacji:
- 2006
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
opioid activity profile in vitro
cyclic dermorphin analogues
opioid peptides
ring-closing metathesis
dermorphin - Opis:
- The dermorphin-derived cyclic tetrapeptide analogues H-Tyr-c[d-Cys-Phe-Cys]NH2 and H-Tyr-c[d-Cys-Phe-D-Cys]NH2 are opioid agonists at the µ and δ receptor. To enhance the metabolic stability of these peptides, we replaced the disulfide bridge with a bis-methylene moiety. This was achieved by solid-phase synthesis of the linear precursor peptide containing allylglycine residues in place of the Cys residues, followed by ring-closing metathesis. In the case of the peptide with L-configuration in the 4-position both the cis and the trans isomer of the resulting olefinic peptides were formed, whereas the cis isomer only was obtained with the peptide having the d-configuration in position 4. Catalytic hydrogenation yielded the saturated -CH2-CH2- bridged peptides. In comparison with the cystine-containing parent peptides, all olefinic peptides showed significantly reduced µ and δ agonist potencies in the guinea pig ileum and mouse vas deferens assays. The -CH2-CH2-bridged peptide with l-configuration in the 4-position was equipotent with its cystine-containing parent in both assays, whereas the bis-methylene analogue with d-configuration in position 4 was 10-27-fold less potent compared to its parent. The effect of the disulfide replacements with the -CH=CH- and-CH2-CH2- moieties on the conformational behavior of these peptides was examined by theoretical conformational analysis which provided plausible explanations in terms of structural parameters for the observed changes in opioid activity.
- Źródło:
-
Acta Biochimica Polonica; 2006, 53, 1; 73-76
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł