Design of MHC Class II (DR4) ligands using conformationally restricted imino acids at p3 and p5

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 16, 1996, Pages 1931-1936

  Hanson, Gunnar J ^a   Vuletich, Jennifer L ^a   Bedell, Louis J ^a   Bono, Christine P ^a   Howard, Susan C ^a   Welply, Joseph K ^a   Woulfe, Susan L ^a   Zacheis, Michelle L ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HA 306 318; LIGAND; MAJOR HISTOCOMPATIBILITY ANTIGEN; OLIGOPEPTIDE; SC 64762; SC 67655; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG STABILITY; ENZYME LINKED IMMUNOSORBENT ASSAY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; PEPTIDE SYNTHESIS; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RHEUMATOID ARTHRITIS;

EID: 0030594982     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00348-4     Document Type: Article

References (12)

1. 1. Nagy, Z. A.; Vidovic, D.; Annual Reports in Medicinal Chemistry 1995, Vol.30, pp 199-208, and references contained therein.
2. 2. Winchester, R. Adv. Immunol. 1994, 56, 389.
3. 3. Hammer, J.; Belunis, C.; Bolin, D.; Papadopoulos, J.; Walsky, R.; Higelin, J; Danho, W.; Sinigaglia, F.; Nagy, Z. A. Proc. Natl. Acad. Sci. USA 1994, 91, 4456, and references contained therein,
4. 50 results presented are the average of 2-5 determinations.
5. 5. Hammer, J.; Gallazzi, F.; Bono, E.; Karr, R. W.; Guenot, J.; Valsasnini, P.; Nagy, Z. A.; Sinigaglia, F.; J. Exp. Med. 1995,181,1847. Also: Woulfe, S. L.; Bono, C. P.; Zacheis, M. L.; Kirschmann, D. A.; Baudino, T. A.; Karr, R. W.; Swearingen, C.; Schwartz, B. D. Arth.. Rheum. 1995,38: 1744.
6. 5. Hammer, J.; Gallazzi, F.; Bono, E.; Karr, R. W.; Guenot, J.; Valsasnini, P.; Nagy, Z. A.; Sinigaglia, F.; J. Exp. Med. 1995,181,1847. Also: Woulfe, S. L.; Bono, C. P.; Zacheis, M. L.; Kirschmann, D. A.; Baudino, T. A.; Karr, R. W.; Swearingen, C.; Schwartz, B. D. Arth. Rheum. 1995,38: 1744.
7. 6. Stern, L. J.; Brown, J. H.; Jardetzky, T. S.; Gorga, J. C.; Urban, R, G.; Strominger, J. L.; Wiley, D. C. Nature (Lond.) 1994, 368, 215. (Coordinates were provided by L. J. Stern, Harvard University, Cambridge, MA).
8. 7. Smith, A. B., III; Hirschmann, R.; Pasternak, A.; Akaishi, R.; Guzman, M. C.; Jones, D. R.; Keenan, T. P.; Sprengeler, P. A. J. Med. Chem. 1994, 37, 215.
9. 8. The dihedral angle measurements for HA306-318 peptide were obtained from reference 6. All other measurements were determined from modeling studies using the MacroModel (v4.5) implementation of MM2.
10. 9. Hanson, G. J.; Clare, M.; Summers, N. L.; Lim, L. W.; Neidhart, D. J.; Shieh, H. S.; Stevens, A. M. Bioorganic and Medicinal Chemistry 1994, 2, 909.
11. 1H NMR, mass spectra) consistent with their structures, and were determined to be pure by HPLC as well as TLC analysis (silica F-254 plates, eluting with chloroform/methanol/water/acetic acid 64 : 30 : 4 : 2). (figure presented) 1) EDC, HOBt, DIEA, methylene chloride 2) 1.6 M ammonium formate in HOAc 20% palladium hydroxide-C 10% Pd-C, rt, 3 hours ↓ SC-67655 70% yield
12. 11. Woulfe, S. L.; Bono, C. P.; Zacheis, M. L.; Welply, J. K.; Kirschmann, D. A.; Baudino, T. A.; Wang, Y.; Stone, D. A.; Hanson, G. J.; Vuletich, J. L.; Bedell, L. J.; Schwartz, B. D.; Howard, S. C. (manuscript in preparation).