A simple multiple release system for combinatorial library and peptide analysis

Tetrahedron Letters

Volumn 37, Issue 1, 1996, Pages 135-138

  Cardno, Marianne ^a   Bradley, Mark ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; PEPTIDE MAPPING; PROTEIN ANALYSIS; TECHNIQUE;

EID: 0030047837     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(95)02092-6     Document Type: Article

References (17)

1. Gallop, M.A., Barrett, R.W., Dower, W.J., Fodor, S.P.A., Gordon, E.M., J. Med. Chem., 1994, 37, 1233-1251.
2. Furka, A., Sebestyen, F., Asgedom, M., Dibo, G., Int. J. Pept. Prot. Res., 1991, 37, 487-493.
3. Bayer, E., Angewandte Chemie, 1991, 30, 113-216.
4. Kania, R.S., Zuckermann, R.N., Marlowe, C.K., J. Am. Chem. Soc., 1994, 116, 8835-8836.
5. Freier, S.M., Konings, D.A.M., Wyatt, J.R., Ecker, D.J., J. Med. Chem., 1995, 38, 344-352
6. Lebl, M., Patek, M., Kocis, P., Krchnak, V., Hruby, V.J., Salmon, S.E., Lam, K.S., Int. J. Pept. Prot. Res., 1993, 41, 201-203 and Salmon, S.E., Lam, K.S., Lebl, M., Kandola, A., Khattri, P.S., Wade, S., Patek, M., Kocis, P., Krchnak, V., Thorpe, D., Felder, S., Proc. Natl. Acad. Sci., 1993, 90, 11708-11712.
7. Lebl, M., Patek, M., Kocis, P., Krchnak, V., Hruby, V.J., Salmon, S.E., Lam, K.S., Int. J. Pept. Prot. Res., 1993, 41, 201-203 and Salmon, S.E., Lam, K.S., Lebl, M., Kandola, A., Khattri, P.S., Wade, S., Patek, M., Kocis, P., Krchnak, V., Thorpe, D., Felder, S., Proc. Natl. Acad. Sci., 1993, 90, 11708-11712.
8. Mitchell, A.R., Kent, S.B.H., Engelhard, M., Merrifield, R.B., J. Org. Chem., 1978, 43, 2845-2852.
9. Experiments showed linker 2 coupled at a slower rate than linkers 3 and 4. In order to incorporate the desired substitution level of linker 2, 1/3 eq of 2 was coupled to the amino methyl resin 1 using DIC/HOBt in DMF prior to coupling of 1/3eq each of linkers 3 and 4. Ninhydrin test was negative at this stage. Esterification was carried out in DCM using DCC and DMAP (1%) for 12 hours.
10. Fields, G.B., Noble, R.L., Int. J. Pep. Prot. Res., 1990, 35, 161-214.
11. Egner, B.J., Langley, G.J., Bradley, M., J. Org. Chem., 1995, 60, 2652-2653.
12. 1H nmr data were consistent with the expected peptide. Fmoc removal and Edman sequencing of (9) gave the expected amino acid sequence.
13. 10
14. Youngquist, R.S., Fuentes, G.R., Lacey, M.P., Keouugh, T., J. Am. Chem. Soc., 1995, 117, 3900-3906.
15. The ratios of peptide released from (6) were provided by quantitative ninhydrin and amino acid analysis before and after cleavage. Ninhydrin analysis gave values of 0.286mmol/g, 0.188mmol/g and 0.071mmol/g (taking into account the lysine residue), to give the ratios of released and attached peptides as approximately 1:1:0.8. Amino acid analysis gave the ratios of amino acids and the degree of substitution as Gly(1.0), Ala(1.0), Lys(1.0), 0.257mmol/g, Gly(1.0), Ala(0.9), Lys(1.1), 0.136mmol/g and Gly(1.1), Ala (0.9), Lys(1.0), 0.04mmol/g (approx. ratio of released and attached peptide 9:7:4)
16. Bernatowicz, M.S., Daniels, S.B., Köster, H., Tetrahedron Lett., 1989, 30, 4645-48.
17. For recent advances in photo-cleavable linkers see Holmes, C.P., Jones, D.G., J. Org. Chem., 1995, 60, 2318-2319.