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Synlett 2012; 23(13): 1937-1940
DOI: 10.1055/s-0031-1290403
DOI: 10.1055/s-0031-1290403
letter
Synthesis, Antibacterial Activity and Cytotoxicity of Novel Janus Peptide Dendrimers
Further Information
Publication History
Received: 13 April 2012
Accepted after revision: 06 May 2012
Publication Date:
16 July 2012 (online)
Abstract
In an attempt to find new antibacterial agents, a series of well-defined Janus peptide dendrimers, which feature multiple anionic groups and amphiphilic structure, were synthesized and characterized in detail. The antibacterial activities of all the synthesized dendrimers were tested and screened by using the two-fold serial dilution method. Several compounds showed activity against E. coli, S. aureus, methicillin-resistant S. aureus, and E. faecalis. Further cytotoxicity assays showed that the antibacterial dendrimers were nontoxic against HEK293.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
Included are detailed synthetic procedures and characterization data, as well as methods
for antibacterial and toxicity experiments.
- Supporting Information
-
References and Notes
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- 19 Synthesis of Janus Dendrimers; Typical Procedure for 2a: Compound 7 (313 mg, 0.5 mmol) dissolved in anhyd THF (25 mL) was cooled to –15 °C, and NMM (10 mmol) and IBCF (10 mmol) were added. After stirring for 10 min, 4a (900 mg, 0.5 mmol) dissolved in anhyd THF (10 mL) was added dropwise. The reaction mixture was vigorously stirred at r.t. for 24 h, then the solution was concentrated under vacuum, and the residue was taken up in EtOAc (30 mL) and washed with 1 M HCl (10 mL), 1 M NaHCO3 (10 mL), and brine (10 mL). The organic layer was dried over anhyd Na2SO4. After concentration, the residue was purified by silica gel column chromatography (CH2Cl2–MeOH) to obtain a white waxy solid. Pd/C (10%, 100 mg) was added to a solution of the obtained white waxy solid in MeOH–CH2Cl2 (30 mL, 3:1 v/v). The reaction mixture was stirred under a hydrogen atmosphere for 24 h, filtered through a membrane filter, and concentrated under reduced pressure to afford 2a (539 mg, 64%) as a white foam. 1H NMR (400 MHz, DMSO-d 6): δ = 0.83–0.87 (t, J = 6.4 Hz, 6 H, 2 × CH3), 1.23 (br s, 40 H, myristic acid 20 × CH2), 1.48–1.49 (m, 4 H, myristic acid-β-CH 2 × 2), 2.24–2.35 (m, 8 H, myristic acid-α-CH 2 × 2 + Asp-β-CH 2/2 × 4), 2.38–2.59 (m, 16 H, succinic acid CH 2 × 2 + NCH2CH 2CONH × 6), 2.63–2.70 (m, 4 H, Asp-β-CH 2/2 × 4), 3.41–3.60 (m, 16 H, NCH 2CH2O × 3 + NCH 2CH2CONH × 3), 3.99 (br s, 6 H, Gly-CH 2 × 3), 4.05–4.18 (m, 4 H, NCH2CH 2O × 2), 4.48–4.54 (m, 4 H, Asp-α-CH × 4), 7.89 (br s, 1 H, CONH), 7.96 (br s, 1 H, CONH), 8.10 (br s, 1 H, CONH), 8.25 (br s, 1 H, CONH), 8.27 (br s, 1 H, CONH), 8.39 (br s, 1 H, CONH), 8.41 (br s, 1 H, CONH), 12.64 (br s, 8 H, Asp-COOH × 8). MS (ESI): m/z [M + Na + H]+ calcd for C76H123N11O31: 1685.84; found: 1709.5. Anal. Calcd for C76H123N11O31: C, 54.11; H, 7.35; N, 9.13; O, 29.40. Found: C, 54.03; H, 7.26; N, 9.01; O, 29.31. Detailed characterization data of 1a, 1b, and 2b are provided in the Supporting Information (see S1 for details)
- 20 Methods for antibacterial and toxicity experiments are given in the Supporting Information (see S2 for details)
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