Total synthesis of a reversed-bacicyclin using a combination of solid- and solution-phase methods

Rani, Maharani and Anastasya, Firdausi and Tri, Mayanti and Desi, Harneti and Nurlelasari, Nurlelasari and Safri, Ishmayana and Kindi, Farabi and Unang, Supratman and Ace, Tatang Hidayat (2022) Total synthesis of a reversed-bacicyclin using a combination of solid- and solution-phase methods. Indonesian Journal of Chemistry (Indones. J. Chem), 22 (4): 16. pp. 1061-1069. ISSN 1411-9420 e_ISSN: 2460-1578

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Bacicyclin is a cyclic hexapeptide with antibacterial activity against Enterococcus faecalis and Staphylococcus aureus with Minimum Inhibition Concentration (MIC) values of 8 and 12 µM, respectively. Studies on a reversed sequence of bacicyclin were conducted to investigate how the reversed peptide sequence affects its biological properties. A reversed-bacicylin, cyclo-(Gly-Leu-Val-Ile-Ala-Phe), was successfully synthesized by constructing the linear precursor on 2-chlorotrityl chloride resin using a Fmoc-based strategy. The HATU/HOAt reagent was applied in all peptidic bond formations, and the desired linear hexapeptide (82% yield) was cleaved off the resin using a mixture of trifluoroacetic acid:dichloromethane (2:8). The linear peptide was cyclized using 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxidehexa-fluorophosphate (HATU) as a coupling agent and diisopropylethylamine (DIPEA) as the base in a very dilute solution (0.001 M) in dichloromethane, then purified by octadecyl silica gel (ODS) column chromatography to obtain the reversed-bacicyclin (43.7% yield). The purity of the cyclic product was analyzed using analytical RP-HPLC (tR = 20.01 min), and characterized by HR-TOF-MS, 1H-NMR, and 13C-NMR. The biological activity of the reversed-bacicyclin is much lower compared to bacicyclin, indicating that the amino acid sequence of the cyclopeptide dictates the antibacterial activity. This finding gives additional information on the relationship between peptide sequence and biological properties.

Item Type: Article
Uncontrolled Keywords: Bacicyclin, Solid-phase peptide synthesis, Cyclisation, Cyclic hexapeptide antibacterial peptide
Subjects: Medicine & Biology
Medicine & Biology > Biochemistry
Medicine & Biology > Microbiology
Medicine & Biology > Pharmacology & Pharmacological Chemistry
Chemistry > Basic & Synthetic Chemistry
Depositing User: Djaenudin djae Mohamad
Date Deposited: 12 May 2023 05:39
Last Modified: 12 May 2023 05:39

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