Application of a trifunctional reactive linker for the construction of antibody-drug hybrid conjugates

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 21, 2008, Pages 5785-5788

  Thomas, Joshua D ^a   Hofer, Thomas ^b   Rader, Christoph ^b   Burke Jr , Terrence R ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Fc; IgG1; Immunoconjugate; Integrin; LLP2A; Peptidomimetic

Indexed keywords

ANTIBODY CONJUGATE; BIOTIN; FC RECEPTOR; IMMUNOGLOBULIN FC FRAGMENT; LYSINE; MACROGOL; MALEIMIDE; PEPTIDE DERIVATIVE; SELENOCYSTEINE; SUCCINAMIDE; SUCCINIC ACID DERIVATIVE; UNCLASSIFIED DRUG; VERY LATE ACTIVATION ANTIGEN 4;

ANTIBODY ENGINEERING; ARTICLE; DRUG CONJUGATION; DRUG TARGETING; REACTION ANALYSIS; RECEPTOR BINDING; SOLID PHASE SYNTHESIS;

ANTIBODIES; ENZYME-LINKED IMMUNOSORBENT ASSAY; IMMUNOCONJUGATES; MOLECULAR MIMICRY; MOLECULAR STRUCTURE; PHARMACEUTICAL PREPARATIONS;

EID: 53949113568     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.09.078     Document Type: Article

References (24)

1. Wu A.M., and Senter P.D. Nat. Biotechnol. 23 (2005) 1137
2. Ricart A.D., and Tolcher A.W. Nat. Clin. Pract. Oncol. 4 (2007) 245
3. Rader C., Sinha S.C., Popkov M., Lerner R.A., and Barbas III C.F. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 5396
4. Popkov M., Rader C., Gonzalez B., Sinha S., and Barbas III C. Int. J. Cancer 119 (2006) 1194
5. Doppalapudi V., Tryder N., Li L., Aja T., Griffith D., Liao F., Roxas G., Ramprasad M., Bradshaw C., and Barbas III C. Bioorg. Med. Chem. Lett. 17 (2007) 501
6. Hofer T., Thomas J.D., Burke Jr. T.R., and Rader C. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 12451
7. Peng L., Liu R., Marik J., Wang X., Takada Y., and Lam K.S. Nat. Chem. Biol. 2 (2006) 381
8. Holzmann B., Gosslar U., and Bittner M. Curr. Top. Microbiol. Immunol. 231 (1998) 125
9. Jin H., Su J., Garmy-Susini B., Kleeman J., and Varner J. Cancer Res. 66 (2006) 2146
10. Matsunaga T., Takemoto N., Sato T., Takimoto R., Tanaka I., Fujimi A., Akiyama T., Kuroda H., Kawano Y., Kobune M., Kato J., Hirayama Y., Sakamaki S., Kohda K., Miyake K., and Niitsu Y. Nat. Med. 9 (2003) 1158
11. Langer-Gould A., Atlas S., Green A., Bollen A., and Pelletier D. N. Engl. J. Med. 353 (2005) 375
12. Berger J., and Koralnik I. N. Engl. J. Med. 353 (2005) 414
13. Drazen J. N. Engl. J. Med. 353 (2005) 417
14. Olson D.L., Burkly L.C., Leone D.R., Dolinski B.M., and Lobb R.R. Mol. Cancer Ther. 4 (2005) 91
15. Carpenter R.D., Andrei M., Lau E.Y., Lightstone F.C., Liu R., Lam K.S., and Kurth M.J. J. Med. Chem. 50 (2007) 5863
16. Song A., Wang X., Zhang J., Marik J., Lebrilla C.B., and Lam K.S. Bioorg. Med. Chem. Lett. 14 (2004) 161
17. Thushim G., Hersel U., Goodman S.L., and Kessler H. Chem. Eur. J. 9 (2003) 2717
18. A biotin label was required for determining the half-life of free and conjugated LLP2A in mice (see Ref. 6).
19. Robey F.A., and Fields R.L. Anal. Biochem. 177 (1989) 373
20. Zuckermann R.N., Kerr J.M., Kent S.B., and Moos W.H. J. Am. Chem. Soc. 114 (1992) 10646
21. +). Found: 1904.9622.
22. 2O (10× 200 μL/well), colorimetric detection was performed using 2,2′-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (Roche) as substrate according to the manufacturer's directions.
23. 5 cells were distributed into wells of a V-bottom 96-well plate (Corning). The cells were then incubated with Fc-Sec-LLP2A, Fc-Stop, and 2e (1 h, 0 °C). After washing twice with 1% (v/v) FCS/PBS, the cells were incubated with a 1:20 dilution of Cy5-conjugated rabbit anti-human IgG (1 h, 0 °C). After washing twice as above, the cells were resuspended in FCS/PBS (400 μL 1% v/v) and analyzed using a FACScan instrument (Becton-Dickinson).
24. 1 antibody (R&D Systems) (both 10 μg/mL) (1 h, 0 °C). Cells were washed and a 1:25 dilution of PE-coupled streptavidin (BD Biosciences) was added. After washing twice as before, the cells were resuspended in FCS/PBS (400 μL 1% v/v) and analyzed using a FACScan instrument (Becton-Dickinson).