Peptide based inhibitors of interleukin-8: Structural simplification and enhanced potency

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 4, 1997, Pages 429-432

  Attwood, Michael R ^a   Conway, Elizabeth A ^a   Dunsdon, Rachel M ^a   Greening, John R ^a   Handa, Balraj K ^a   Jones, Philip S ^a   Jordan, Steven C ^a   Keech, Elizabeth ^a   Wilson, Francis X ^a  

^a ROCHE PRODUCTS LTD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 8; INTERLEUKIN 8 RECEPTOR; INTERLEUKIN RECEPTOR; PEPTIDE; PSEUDOPEPTIDE;

ARTICLE; CHEMICAL MODIFICATION; DRUG DESIGN; DRUG SYNTHESIS; MOLECULAR WEIGHT; RECEPTOR BINDING; STRUCTURE ACTIVITY RELATION;

EID: 0031576831     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00036-X     Document Type: Article

References (11)

1. 1. Oppenheim, J.J.; Zachariae, C.O.C.; Mukaida, N.; Matsushima, K. Annu. Rev. Immunol., 1991, 9, 617-48.
2. 2. Koch, A.E.; Kunkel, S.E.; Burrows, J.C.; Evanoff, H.L.; Haines, G.K.; Pope, R.M.; Streiter, R.M. J. Immunol., 1991, 147, 2187.
3. 3. a) Mulligan, M.S.; Jones, M.L.; Bolanski, M.A.; Baganoff, M.P.; Deppeler, C.L., Meyers, D.M.; Ryan, U.S.; Ward, P.A. J. Immunol., 1993, 150, 5585.
4. b) Sekido, N.; Mukaida, N.; Harada, A.; Nakanishi, I.; Watanabe, Y.; Matsushima, K. Nature (London), 1993, 365, 654.
5. 4. Attwood, M.R.; Borkakoti, N.; Bottomley, G.A.; Conway, E.A.; Cowan, I.; Fallowfield, A.G.; Handa, B.K.; Jones, P.S.; Keech, E.; Kirtland, S.J.; Williams, G.; Wilson, F.X. Biorg. Med. Chem. Lett., 1996, 6, 1869.
6. 5. For assay details see Ref. 4.
7. 6. Evans, D.A; Bilodeau, M.T.; Somers, T.C.; Clardy, J.; Cherry, D.; Kato, Y. J.Org.Chem., 1991, 56, 5750.
8. 7. Davies, S.G.; Ichihara, O. Tetrahedron Asymm., 1991, 2, 183.
9. 8 Bolin, D.R.; Sytwu, I-I.; Humiec, F.; Meienhofer, J. Int. J. Pept. Protein Res., 1989, 33, 353.
10. 9 Rodriguez, M.; Aumelas, A.; Martinez, J. Tetrahedron Lett., 1990, 36, 5153.
11. 10. Peptides were synthesised using a Milligen 9050 peptide synthesiser under continuous flow conditions employing Fmoc chemistry on PepsynK resin with AM linker. They were synthesised as N-terminal acetyl and C-terminal amides to prevent unwanted charged interactions at the termini. Resin cleavage conditions were TFA:phenol:EDT:anisole (95:2.5:2.5:2.5) 2h, RT. The resin was filtered and the solvent removed. The peptide was precipitated in ether, filtered and dried. Purification was by RP-HPLC on an Aquapore octyl column (20micron, 100mmx10mm).The elution gradient comprised 95%A-95%B over 15min where A=0.1%TFA in water and B=0.085%TFA in 70%acetonitrile. The peptides were checked for purity by analytical RP-HPLC and structures were validated by mass spectrometry, 1H NMR and amino acid analysis.