Toward the Synthesis and Improved Biopotential of an N-methylated Analog of a Proline-Rich Cyclic Tetrapeptide from Marine Bacteria

Authors

Rajiv Dahiya, The University of the West Indies
Suresh Kumar, Kurukshetra University
Suhkbir Lal Khokra, Kurukshetra University
Sheeba Varghese Gupta, University of South FloridaFollow
Vijaykumar B. Sutariya, University of South FloridaFollow
Deepak Bhatia, Shenandoah University
Ajay Sharma, Amity University
Shamjeet Singh, The University of the West Indies
Sandeep Maharaj, The University of the West Indies

Document Type

Article

Publication Date

8-2018

Keywords

N-methylation, tetracyclopeptide, Pseudomonas sp., macrocyclization, marine sponge, Pseudoalteromonas sp., solution-phase peptide synthesis, pharmacological activity

Digital Object Identifier (DOI)

https://doi.org/10.3390/md16090305

Abstract

An N-methylated analog of a marine bacteria-derived natural proline-rich tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments Boc-l-prolyl-l-N-methylleucine-OH and l-prolyl-l-N-methylphenylalanine-OMe. A coupling reaction was accomplished utilizing N,N′-Dicyclohexylcarbodidimde (DCC) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC·HCl) as coupling agents and Triethylamine (TEA) or N-methylmorpholine (NMM) as the base in the presence of the racemization suppressing agent. This was followed by the cyclization of the linear tetrapeptide fragment under alkaline conditions. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FTIR (Fourier-transform infrared spectroscopy), ¹H NMR (Nuclear magnetic resonance spectroscopy), ¹³C NMR, and mass spectrometry. From the bioactivity results, it was clear that the newly synthesized proline-rich tetracyclopeptide exhibited better anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus eugeniae at a concentration of 2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N-methylated tetracyclopeptide displayed significant activity against pathogenic Candida albicans.

Rights Information

This work is licensed under a Creative Commons Attribution 4.0 License.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Marine Drugs, v. 16, issue 9, art. 305

Scholar Commons Citation

Dahiya, Rajiv; Kumar, Suresh; Lal Khokra, Suhkbir; Varghese Gupta, Sheeba; Sutariya, Vijaykumar B.; Bhatia, Deepak; Sharma, Ajay; Singh, Shamjeet; and Maharaj, Sandeep, "Toward the Synthesis and Improved Biopotential of an N-methylated Analog of a Proline-Rich Cyclic Tetrapeptide from Marine Bacteria" (2018). Pharmacy Faculty Publications. 58.
https://digitalcommons.usf.edu/pharm_facpub/58