کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2005803 | 1541698 | 2016 | 6 صفحه PDF | دانلود رایگان |
• A novel conopeptide with 11 residues was isolated and synthesized.
• Only two and one residues were allocated at loop1 and loop2 of “CCCC”, respectively.
• Im10A showed a ribbon structure with disulfide connectivity “I–IV, II–III”.
• Im10A exhibited moderate analgesic activity.
• The new motif was useful for the future development of biomimetic compounds.
In the present study, we isolated, synthesized and NMR structurally characterized a novel conopeptide Im10A consisting of 11 amino acids (NTICCEGCMCY-NH2) from Conus imperialis. Unlike other conopeptides with four cysteine residues, Im10A had only two residues in loop 1 and one residue in loop 2 (CC-loop1-C-loop2-C), which formed a stable disulfide connectivity “I-IV, II- III” (framework X) with a type I β-turn. Interestingly, Im10A exhibited 50.7% analgesic activity on rat partial sciatic nerve ligation (PNL) at 2 h after Im10A administration. However, 10 μM Im10A exhibited no apparent effect on neuronal nicotinic acetylcholine receptor, and it did not target DRG voltage-dependent sodium, potassium and calcium ion channels and opioid receptor. To our knowledge, Im10A had the most concentrated disulfide bridges among conopeptides with four cysteine residues. This finding provided a new motif for the future development of biomimetic compounds.
Journal: Peptides - Volume 81, July 2016, Pages 15–20