Ureido-based peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase: An investigation of inhibitor bioactive conformation

Journal of Medicinal Chemistry

Volumn 39, Issue 11, 1996, Pages 2178-2187

  Moss, Neil ^a,b   Beaulieu, Pierre ^a   Duceppe, Jean Simon ^a   Ferland, Jean Marie ^a   Gauthier, Jean ^a   Ghiro, Elise ^a   Goulet, Sylvie ^a   Guse, Ingrid ^a   Llinàs Brunet, Montse ^a   Plante, Raymond ^a   Plamondon, Louis ^a   Wernic, Dominik ^a   Déziel, Robert ^a  

^a BOEHRINGER INGELHEIM CANADA LTD   (Canada)

^b BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; ENZYME INHIBITOR; RIBONUCLEOTIDE REDUCTASE;

AMINO TERMINAL SEQUENCE; ARTICLE; DRUG CONFORMATION; DRUG POTENCY; DRUG PROTEIN BINDING; ENZYME INHIBITION; HERPES SIMPLEX VIRUS; HYDROGEN BOND; NONHUMAN; STRUCTURE ACTIVITY RELATION; VIRUS INHIBITION;

ENZYME INHIBITORS; INDICATORS AND REAGENTS; KINETICS; MACROMOLECULAR SUBSTANCES; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR STRUCTURE; OLIGOPEPTIDES; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; RIBONUCLEOTIDE REDUCTASES; SIMPLEXVIRUS; SPECTROMETRY, MASS, FAST ATOM BOMBARDMENT; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

EID: 15844371020     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950825x     Document Type: Article

References (29)

1. Cory, J. G. Role of ribonucleotide reductase in cell division. In Inhibitors of Ribonucleoside Diphosphate Reductase Activity; Cory, J. G., Cory, A. H., Eds.; Pergamon Press Inc.: New York, 1989; pp 1-17.
2. Filatov, D.; Ingemarson, R.; Graslund, A.; Thelander, L. The role of herpes simplex virus ribonucleotide reductase small subunit carboxyl terminus in subunit interaction and formation of iron-tyrosyl center structure. J. Biol. Chem. 1992, 267, 15816-15822.
3. (a) Dutia, B. M.; Frame, M. C.; Subak-Sharpe, J. H.; Clarke, W. N.; Marsden, H. S. Specific inhibition of herpes virus ribonucleotide reductase by synthetic peptides. Nature 1986, 321, 439-441.
4. (b) Cohen, E. A.; Gaudreau, P.; Brazeau, P.; Langelier, Y. Specific inhibition of herpes simplex virus ribonucleotide reductase activity by a nonapeptide derived from the carboxyl terminus of subunit 2. Nature 1986, 321, 441-443.
5. Cosentino, G.; Lavallée, P.; Rakhit, S.; Plante, R.; Gaudette, Y.; Lawetz, C.; Whitehead, P. W.; Duceppe, J.-S.; Lépine-Frenette, C.; Dansereau, N.; Guilbault, C.; Langelier, Y.; Gaudreau, P.; Thelander, L.; Guindon, Y. Specific inhibition of ribonucleotide reductases by peptides corresponding to the C-terminal of their second subunit. Biochem. Cell Biol. 1991, 69, 79-83.
6. Liuzzi, M.; Déziel, R.; Moss, N.; Beaulieu, P.; Bonneau, A.-M.; Bousquet, C.; Chafouleas, J. G.; Garneau, M.; Jaramillo, J.; Krogsrud, R. L.; Lagacé, L.; McCollum, R. S.; Nawoot, S.; Guindon, Y. A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. Nature 1994, 372, 695-698.
7. Moss, N.; Déziel, R.; Adams, J.; Aubry, N.; Bailey, M.; Baillet, M.; Beaulieu, P.; DiMaio, J.; Duceppe, J.-S.; Ferland, J.-M.; Gauthier, J.; Ghiro, E.; Goulet, S.; Grenier, L.; Lavallée, P.; Lépine-Frenette, C.; Plante, R.; Rakhit, S.; Soucy, F.; Wernic, D.; Guindon, Y. Inhibition of herpes simplex virus type 1 ribonucleotide reductase by substituted tetrapeptide derivatives. J. Med. Chem. 1993, 36, 3005-3009.
8. Ulin, U.; Eklund, H. Structure of ribonucleotide reductase protein R1. Nature 1994, 370, 533-539.
9. Bushweller, J. H.; Bartlett, P. A. Investigation of an octapeptide inhibitor of escherichia coli ribonucleotide reductase by transferred nuclear Overhauser effect spectroscopy. Biochemistry 1991, 30, 8144-8150.
10. Moss, N.; Déziel, R.; Ferland, J.-M.; Goulet, S.; Jones, P.-J.; Leonard, S. F.; Pitner, T. P.; Plante, R. Herpes simplex virus ribonucleotide reductase subunit association inhibitors: the effect and conformation of β-alkylated aspartic acid derivatives. Bioorg. Med. Chem. 1994, 2, 959-970.
11. Gaudreau, P.; Paradis, H.; Langelier, Y.; Brazeau, P. Synthesis and inhibitory potency of peptides corresponding to the subunit 2 C-terminal region of herpes virus ribonucleotide reductase. J. Med. Chem. 1990, 33, 723-730.
12. Moss, N.; Beaulieu, P.; Duceppe, J.-S.; Ferland, J.-M.; Gauthier, J.; Ghiro, E.; Goulet, S.; Grenier, L.; Llinas-Brunet, M.; Plante, R.; Wernic, D.; Déziel, R. Peptidomimetic inhibitors of HSV ribonucleotide reductase: a new class of antiviral agents. J. Med. Chem. 1995, 38, 2723-2730.
13. Chou, P. Y.; Fasman, D. G. Prediction of the secondary structure of proteins from their amino acid sequence. Adv. Enzymol. 1978, 47, 45-148.
14. A full account of the NMR-derived solution structure of these compounds and others will be published separately.
15. Unpublished observation.
16. 1,3 strain between the two backbone amides likely destabilizes the alternate chair form. A slight twisting of the chair conformations shown for compounds 16-18 may exist, but this should not invalidate the general conclusions made.
17. Pardi, J.; Billeter, M.; Wüthrich, K. Calibration of the angular dependence of the amide proton-Cα proton coupling constants in a globular protein. J. Mol. Biol. 1984, 180, 741-751.
18. Krogsrud, R. L.; Welchner, E.; Scouten, E.; Liuzzi, M. A solid-phase assay for the binding of peptidic subunit association inhibitors to the herpes simplex virus ribonucleotide reductase large subunit. Anal. Biochem. 1993, 213, 386-390.
19. Kepner, R. E.; Winstein, S.; Young, W. G. Allylic rearrangements. XXIV. Abnormal bimolecular substitution. The condensation of butenyl and pentenyl chlorides with sodium malonic ester. J. Am. Chem. Soc. 1949, 71, 114-119.
20. Monoester hydrolysis of related derivatives is known to be nonselective. Gmeiner, P.; Feldman, P. L.; Chu-Moyer, M. Y.; Rapoport, H. An efficient and practical total synthesis of (+)-vicamine from L-aspartic acid. J. Org. Chem. 1990, 55, 3068-3074.
21. Johansen, J. E.; Christie, B. D.; Rapoport, H. Iminium salts from α-aminoacid decarbonylation. Application to the synthesis of octahydroindolo[2,3-a]quinolizines. J. Org. Chem. 1981, 46, 4914-4920.
22. Röder, E.; Wiedenfeld, H.; Bourauel, T. Synthese von 2,3-Bis-(ethoxycarbonyl)-1H-pyrrol-1-propionsäure-ethylester. Liebigs Ann. Chem. 1987, 1117-1119.
23. A chiral synthesis of the neutral amino acid of compound 34 has been reported. Humphrey, J. M.; Bridges, R. J.; Hart, J. A.; Chamberlin, A. R. 2,3-Pyrrolidinedicarboxylates as neurotransmitter conformer mimics: enantioselective synthesis via chelation-controlled enolate alkylation. J. Org. Chem. 1994, 59, 2469-2472.
24. Polonski, T. Chiroptical properties and molecular geometry of substituted succinic anhydrides and imides. J. Chem. Soc. Perkin Trans. 1 1988, 629-637.
25. Goldesmidt, V. S.; Wick, M. Über peptid-synthesen I. Liebigs Ann. Chem. 1952, 575, 217-231.
26. Valerio, R. M.; Alewood, P. F.; Johns, R. B. Synthesis of optically active 2-(tert-butoxycarbonylamino)-4-dialkyloxyphosphorylbutanoate protected isosteres of O-phosphonoserine for peptide synthesis. Synthesis 1988, 786-789.
27. Zydowsky, T. M.; Dellaria, J. F.; Nellans, H. N. Efficient and versatile synthesis of dipeptide isosteres containing γ- or δ-lactams. J. Org. Chem. 1988, 53, 5607-5616.
28. Déziel, R. Mild palladium(0)-catalyzed deprotection of allyl esters. A useful application in the synthesis of carbapenems and other β-lactam derivatives. Tetrahedron Lett. 1987, 28, 4371-4372.
29. Dess, D. B.; Martin, J. C. Readily accessible 12-1-5 oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. J. Org. Chem. 1983, 48, 4155-4156.