Synthesis of a highly hydrophobic cyclic decapeptide by solid-phase synthesis of linear peptide and cyclization in solution

Chinese Chemical Letters

Volumn 21, Issue 4, 2010, Pages 391-394

  Chen, Jian ^a   Zhang, Bei ^a   Xie, Cao ^a   Lu, Yi ^a   Wu, Wei ^a  

^a FUDAN UNIVERSITY   (China)

Author keywords

Cyclic peptide; Cyclization; cyclo LWLWLWLWLQ ; Decapeptide; Purification; Solid phase synthesis

Indexed keywords

EID: 76349100034     PISSN: 10018417     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cclet.2009.11.026     Document Type: Article

References (20)

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17. Abbreviations for amino acids (l-configuration unless otherwise designated) follows the recommendations of the IUPAC-IUB Commission on Biochemical Nomenclature (Eur. J. Biochem. 138 (1984) 9). Leu and L: Leucine; Trp and W: Tryptophan; Gln and Q: Glutamine; Asp: Aspartic acid; Glu: Glutamic acid. Additional abbreviation used are: AA: amino acids; Boc: tert-Butoxycarbonyl; For: Formyl; PyBOP: Benzotrazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate; HOBt: N-Hydroxybenzotriazloe; DIPEA: N,N-diisopropylethylamine; TFA: trifluoroacetic acid; DMF: N,N-dimethylformamide; DCM: dichloromethane; RP-HPLC: reverse-phase high performance liquid chromatography; NMR: nuclear magnetic resonance; ESI-MS: electrospray ionization-mass spectrometry.
18. Experimental conditions: Synthesis was performed in a 10 mL peptides synthesizer, starting with 110 mg Boc-Trp(For)-PAM resin (loading 0.6 mmol/g) by the standard Boc protocol. The peptide chain was then assembled by consecutive addition of the alternating 5 eq Boc-d-Leu-OH, 3 eq Boc-Trp-OH and 1 eq Boc-Gln-OH according to the PyBOP coupling procedure: 4 eq Boc-amino acid, 4 eq PyBOP, 4 eq HOBt and 8 eq DIPEA in pure DMF for 30 min activation time and 30 min reaction time. Completion of the reaction was monitored by the ninhydrin test. Boc protecting groups were removed by treatment with TFA (50%, v/v in DCM; 15 min; twice), followed by the conventional washing cycles with DCM and DMF. When the last residue was coupled, the For protecting group was subsequently removed by treatment with piperidine (20%, v/v in DMF; 10 min; twice). After being washed well with DCM five times and dried under reduced pressure to remove DCM residues, the resin was treated with 10 mL HF and 5% p-methyl phenol at 0 °C for 1 h. The crude product of decapeptides was extracted in aqueous acetic acid (50%, v/v) and lyophilized. Semi-preparative RP-HPLC was employed to remove by-products.
19. 6): δ 0.65 (d, 30H), 1.0-1.5 (m, 15H), 1.70-2.24 (m, 4H), 2.18-3.28 (m, 10H), 4.0-4.8 (m, 12H), 6.85-7.32 (m, 16H), 7.55-7.62 (m, 4H), 7.76-8.44 (m, 8H), 10.79 (s, 4H).
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