Abstract
The ring-closing metathesis reaction can be used to cross-link allylated serine residues situated at the i and i + 3 positions in 310-helical peptides containing the helicogenic amino acid, ∞-aminoisobutyric acid (Aib). An octapeptide with the sequence Boc-Aib-Aib-Aib-Ser(Al)-Aib-Aib-Ser(Al)-Aib-OMe was found to undergo a facile and >20:1 E-selective ring-closing metathesis (RCM) reaction catalyzed by the Grubbs second-generation catalyst to yield an 18-membered macrocycle. The formation of this cross-link does not significantly disturb the peptide's native 310-helicity, as judged by an X-ray diffraction study of the acyclic diene, the E-olefin RCM product, and its hydrogenated derivative. A heptapeptide system with the sequence Boc-Val-Ser(Al)-Leu-Aib-Ser(Al)-Val-Leu-OMe also underwent an efficient RCM reaction, albeit with diminished E-selectivity. It is apparent from these studies that a minimal, RCM-derived, macrocyclic constraint can be readily incorporated into 310-helical peptides.
Original language | English (US) |
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Pages (from-to) | 6986-6987 |
Number of pages | 2 |
Journal | Journal of the American Chemical Society |
Volume | 129 |
Issue number | 22 |
DOIs | |
State | Published - Jun 6 2007 |
All Science Journal Classification (ASJC) codes
- Catalysis
- General Chemistry
- Biochemistry
- Colloid and Surface Chemistry