Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933

Authors

Xuewen Hou, Ocean University of China
Changlong Li, Ocean University of China
Runfang Zhang, Ocean University of China
Yinping Li, Ocean University of China
Huadong Li, Ocean University of China
Yundong Zhang, Ocean University of China
Han Shen Tae, Illawarra Health and Medical Research Institute
Rilei Yu, Ocean University of China
Qian Che, Ocean University of China
Tianjiao Zhu, Ocean University of China
Dehai Li, Ocean University of China
Guojian Zhang, Ocean University of China

Publication Name

Marine Drugs

Abstract

Chemical investigation of the psychrophilic fungus Pseudogymnoascus sp. HDN17-933 derived from Antarctica led to the discovery of six new tetrapeptides psegymamides A–F (1–6), whose planar structures were elucidated by extensive NMR and MS spectrometric analyses. Structurally, psegymamides D–F (4–6) possess unique backbones bearing a tetrahydropyridoindoles unit, which make them the first examples discovered in naturally occurring peptides. The absolute configurations of structures were unambiguously determined using solid-phase total synthesis assisted by Marfey’s method, and all compounds were evaluated for their inhibition of human (h) nicotinic acetylcholine receptor subtypes. Compound 2 showed significant inhibitory activity. A preliminary structure–activity relationship investigation revealed that the tryptophan residue and the C-terminal with methoxy group were important to the inhibitory activity. Further, the high binding affinity of compound 2 to hα4β2 was explained by molecular docking studies.

Open Access Status

This publication may be available as open access

Volume

20

Issue

10

Article Number

593

Funding Number

2021CXLH0012

Funding Sponsor

National Natural Science Foundation of China-Shandong Joint Fund