In:
International Journal of Peptide and Protein Research, Wiley, Vol. 46, No. 6 ( 1995-12), p. 527-534
Abstract:
Motilin is a 22‐residue peptide stimulating stomach and intestinal motility. The motilin 1–12 fragment displays biological effects similar to the native peptide. Selective reduction of the amide carbonyl groups to form CH 2 NH analogs leads to a significant reduction in activity for the first two N ‐terminal positions and to a complete loss of activity for all other positions. The structures of motilin 1–12 and ten reduced analogs were investigated using the temperature dependence of the amide NH chemical shifts. In all the analogs, the structure of the N ‐terminal region (residues 1–5) was different from the structure of motilin 1–12, which is characterized by hydrogen bonding between Phe 1 and Ile 4 . The structure of the C ‐terminal region of analogs was similar to the structure of moth 1–12 for the first two reduction positions only (1–2 and 2–3), indicating that the C‐terminal portion of motilin 1–12 is more critical for biological activity. Complete structural characterizations of motilin 1–12, [CH 2 NH] 1–2 , and [CH 2 NH] 4–5 ‐motilin 1–12 were performed by two‐dimensional NMR spectroscopy and molecular modeling. The structural features observed confirm the differences based on the temperature dependence of the amide NH chemical shifts. These results demonstrate that conservation of the amide bond rigidity is essential for the activity of non‐hydrolyzable analogs. © Munksgaard 1995.
Type of Medium:
Online Resource
ISSN:
0367-8377
DOI:
10.1111/jpp.1995.46.issue-6
DOI:
10.1111/j.1399-3011.1995.tb01608.x
Language:
English
Publisher:
Wiley
Publication Date:
1995
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