Efficient synthesis of thioether-based cyclic peptide libraries

Tetrahedron Letters

Volumn 39, Issue 45, 1998, Pages 8357-8360

  Roberts, Kade D ^a   Lambert, John N ^a   Ede, Nicholas J ^b   Bray, Andrew M ^b  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b Migenix Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BROMOACETIC ACID; CYCLOPEPTIDE; PEPTIDE LIBRARY; SULFIDE;

ACYLATION; AMINO TERMINAL SEQUENCE; ARTICLE; BROMINATION; CARBOXY TERMINAL SEQUENCE; CHEMICAL BINDING; CHEMICAL REACTION; CYCLIZATION; PEPTIDE SYNTHESIS;

EID: 0032487764     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01843-7     Document Type: Article

References (12)

1. 1. Spatola, A.F., Darlak, K. and Romanovskis, P., Tetrahedron Lett. 1996, 37, 591.
2. 2. Eichler, J., Lucka, A.W. and Houghten, R.A., Peptide Res. 1994, 7, 300.
3. 3. McMurray, J.S., Tetrahedron Lett. 1991, 32, 7679.
4. 4. Tam, P.J. and Pallin, D., J. Chem. Soc. Chem. Commun. 1995, 2021.
5. 5. (a) Robey, F.A. and Fields, R.L., Anal. Biochem., 1989, 177, 373;
6. (b) Virgilio, A.A. and Ellman, J.A., J. Am. Chem. Soc. 1994, 116, 11580.
7. 6. Andreu, D., Albericio, F., Solé, N., Munson, M., Ferrer, M. and Barany, M. Peptide Synthesis Protocols 1-91 (Humana Press, Totowa, NJ, 1994).
8. 7. Bray, A.M., Valerio, R.M., DiPasquale, A.J., Greig, J. and Maeji, J., J. Peptide Science 1995, 1, 80.
9. -1. Details of the chemical nature of these crowns is available at http://www.chirontechnologies.com.au/techn/pub_pdf.htm. Unless otherwise specified, Asp and Lys residues were protected as Asp(OtBu) and Lys(Boc). For Fmoc-AA-OH amino acid couplings, DMF solutions that were 0.1M with respect to Fmoc-AA-OH, HBTU, HOBt and DIPEA were prepared and allowed to stand for 5 minutes prior to addition to the crown supports. The crowns were then agitated gently in the solution for 2 hours at room temperature. For Fmoc-AA-OPfp amino acid couplings, the crowns were rotated in a solution of DMF that was 0.1M with respect to Fmoc-AA-OPfp and HOBt for 2 hours.
10. 9. Crowns were agitated in a solution of 25%DCM/DMF, 0.1M with respect to DIC and 0.2M with respect to α-bromoacetic acid, for 2 hours at room temperature. The solution was activated for 5 minutes before the crowns were added.
11. 2O/MeCN and then freeze dried to give the crude target peptide.
12. 11. Analytical HPLCs were performed using a 100 × 4.6mm Phenomenex Ultremex C18 reverse phase column connected to Waters 510 HPLC pumps and a Waters 996 PDA detector. Gradient elution was from A (0.1%TFA in water) to B(acetonitrile) over 40 minutes. HPLC samples were prepared by dissolving the peptides in 50/50 water/acetonitrile.