虫草七肽A的全合成与药理研究

Total Synthesis and Pharmacological Investigation of Cordyheptapeptide A.

作者信息

Kumar Suresh, Dahiya Rajiv, Khokra Sukhbir Lal, Mourya Rita, Chennupati Suresh V, Maharaj Sandeep

机构信息

Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119, Haryana, India.

Laboratory of Peptide Research and Development, School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad & Tobago, West Indies.

出版信息

Molecules. 2017 May 27;22(6):682. doi: 10.3390/molecules22060682.

DOI:10.3390/molecules22060682

PMID:28554994

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6152760/

Abstract

The present investigation reports the synthesis of a phenylalanine-rich -methylated cyclopeptide, cordyheptapeptide A (), previously isolated from the insect pathogenic fungus sp. BCC 1788, accomplished through the coupling of -methylated tetrapeptide and tripeptide fragments followed by cyclization of the linear heptapeptide unit. Structure elucidation of the newly synthesized cyclopolypeptide was performed by means of FT-IR, ¹H-NMR, C-NMR, and fast atom bombardment mass spectrometry (FABMS), and screened for its antibacterial, antidermatophytic, and cytotoxic potential. According to the antimicrobial activity results, the newly synthesized -Methylated cyclopeptide exhibited potent antibacterial activity against Gram-negative bacteria and and antifungal activity against dermatophytes and at a concentration of 6 μg/mL, in comparison to the reference drugs, gatifloxacin and griseofulvin. In addition, cyclopolypeptide displayed suitable levels of cytotoxicity against (DLA) and (EAC) cell lines.

摘要

本研究报道了一种富含苯丙氨酸的甲基化环肽——虫草七肽A（）的合成，该肽先前从昆虫病原真菌sp. BCC 1788中分离得到，通过甲基化四肽和三肽片段的偶联，随后将线性七肽单元环化来完成合成。通过傅里叶变换红外光谱（FT-IR）、¹H-核磁共振（¹H-NMR）、碳-核磁共振（C-NMR）和快原子轰击质谱（FABMS）对新合成的环多肽进行结构解析，并对其抗菌、抗皮肤真菌和细胞毒性潜力进行筛选。根据抗菌活性结果，与参考药物加替沙星和灰黄霉素相比，新合成的甲基化环肽在浓度为6 μg/mL时，对革兰氏阴性菌和显示出强效抗菌活性，对皮肤真菌和显示出抗真菌活性。此外，环多肽对（DLA）和（EAC）细胞系表现出适度的细胞毒性水平。