A practical approach to orthogonally connected oligopyrrole-peptide conjugates

Tetrahedron Letters

Volumn 40, Issue 18, 1999, Pages 3625-3628

  Vázquez, Eugenio ^a   Caamaño, Ana M ^a   Castedo, Luis ^a   Gramberg, Dieter ^a,b   Mascareñas, José L ^a  

^a UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

bZIP proteins; Distamycin; Oligopyrrole; Solid phase peptide synthesis

Indexed keywords

DISTAMYCIN A; GLUTAMIC ACID; OLIGOPYRROLE; PEPTIDE; PYRROLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; PEPTIDE SYNTHESIS; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

EID: 0033617203     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00491-8     Document Type: Article

References (20)

1. [1] Vázquez E, Caamaño, AM, Castedo L, Mascareñas, JL Tetrahedron Lett., preceeding communication in this issue.
2. [2] Several proteins use major groove and minor groove binding motifs, see for instance: (a) Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO Cell 1994; 77:21-32. (b) Feng JA, Johnson RC, Dickerson RE Science 1994; 263: 348-355. (c) Lo ML, Ha S, Pelczer I, Pal S, Walker S. Proc. Nat. Acad. Sci. USA 1998; 95:8455-8460 A report on the cooperative major-minor groove DNA binding of oligonucleotide-oligopyrrole hybrids has recently appeared: Szewzyk JW, Baird EE, Dervan PB Angew. Chem., Int. Ed. Eng. 1996; 35: 1487-1489.
3. [2] Several proteins use major groove and minor groove binding motifs, see for instance: (a) Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO Cell 1994; 77:21-32. (b) Feng JA, Johnson RC, Dickerson RE Science 1994; 263: 348-355. (c) Lo ML, Ha S, Pelczer I, Pal S, Walker S. Proc. Nat. Acad. Sci. USA 1998; 95:8455-8460 A report on the cooperative major-minor groove DNA binding of oligonucleotide-oligopyrrole hybrids has recently appeared: Szewzyk JW, Baird EE, Dervan PB Angew. Chem., Int. Ed. Eng. 1996; 35: 1487-1489.
4. [2] Several proteins use major groove and minor groove binding motifs, see for instance: (a) Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO Cell 1994; 77:21-32. (b) Feng JA, Johnson RC, Dickerson RE Science 1994; 263: 348-355. (c) Lo ML, Ha S, Pelczer I, Pal S, Walker S. Proc. Nat. Acad. Sci. USA 1998; 95:8455-8460 A report on the cooperative major-minor groove DNA binding of oligonucleotide-oligopyrrole hybrids has recently appeared: Szewzyk JW, Baird EE, Dervan PB Angew. Chem., Int. Ed. Eng. 1996; 35: 1487-1489.
5. [2] Several proteins use major groove and minor groove binding motifs, see for instance: (a) Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO Cell 1994; 77:21-32. (b) Feng JA, Johnson RC, Dickerson RE Science 1994; 263: 348-355. (c) Lo ML, Ha S, Pelczer I, Pal S, Walker S. Proc. Nat. Acad. Sci. USA 1998; 95:8455-8460 A report on the cooperative major-minor groove DNA binding of oligonucleotide-oligopyrrole hybrids has recently appeared: Szewzyk JW, Baird EE, Dervan PB Angew. Chem., Int. Ed. Eng. 1996; 35: 1487-1489.
6. [3] It has been shown that microgonotropenes, which contain tethers attached to these pyrrole nitrogens, can "truck" groups towards the major groove: (a) Bruice TC, Mei HY, He GX, Lopez V Proc. Nat. Acad. Sci USA 1992; 89: 1700-1704. (b) Xue T, Browne KA, Bruice TC. Bioconjugate Chem. 1995; 6: 82-87.
7. [3] It has been shown that microgonotropenes, which contain tethers attached to these pyrrole nitrogens, can "truck" groups towards the major groove: (a) Bruice TC, Mei HY, He GX, Lopez V Proc. Nat. Acad. Sci USA 1992; 89: 1700-1704. (b) Xue T, Browne KA, Bruice TC. Bioconjugate Chem. 1995; 6: 82-87.
8. [4] Ellemberger TE, Brandi CJ, Struhl K, Harrison SC Cell 1992; 71:1223-1237
9. [5] Coll M, Frederick CA, Wang AHJ, Rich A. Proc. Nat. Acad. Sci. USA 1987; 84: 8385-8389.
10. [6] (a) Atherton E, Sheppard RC Solid Phase Peptide Synthesis, a Practical Approach. Oxford: IRL Press, 1989.
11. (b) Merrifield B Solid-Phase Peptide Synthesis. In Gutte B, Editor. Peptides: Synthesis, Strucures and Applications. San Diego: Academic Press, 1995; 94-159.
12. (c) Fields GB, Noble RL Int. J. Peptide. Protein Res. 1990; 35: 161-214.
13. [7] The aminoacids were incorporated with the following protecting groups: Arg(PMC), Asp(OtBu), Cys(Trt), Glu(OtBu), Lys(t-Boc), Ser(tBu), Thr(tBu).
14. +] m/z = 2650.0, calcd: 2649.4.
15. [9] The nitropyrrole 5 was prepared by known procedures: Hale WJ, Hoyt WV J. Am. Chem. Soc. 1915; 37: 2538-2582.
16. [10] We preferred the protection of the secondary amine in order to avoid side reactions. Preliminary experiments involved protection as alloc, but we later found that this group is incompatible with the nitro reduction conditions.
17. 3, 250 MHz) δ 7.64 (s, 1H), 7.35 (s, 1H), 4.33 (t, 2H, J = 6.9 Hz), 3.19 (m, 6H), 1.72-1.68 (m, 2H), 1.49-1.36 (m, 2H), 1.32 (s, 18H). FAB-MS: m/z 397.15 (M-OtBu).
18. [12] He GX, Browne KA, Groppe JC, Blaskó A, Mei HY, Bruice TC J. Am. Chem. Soc. 1993; 115: 7061-7071.
19. 3OD, 250 MHz) δ 7.86 (br s, 1H), 7.80 (s, 1H), 7.31 (s, 1H), 7.15 (br s, 1H), 7.08 (brs, 1H), 6.87 (br s, 1H), 6.79 (br s, 1H), 4.37 (t, 2H, J = 7 Hz), 3.89 (s, 3H), 3.81 (s, 3H), 3.31 (t, 2H, J = 6.3 Hz), 3.21 (s, 3H), 3.20-3.01 (m, 8H), 2.81 (s, 6H), 1.90 (m, 2H), 1.63 (m, 2H), 1.41 (m, 2H), 1.31 (s, 18H). FAB-MS: m/z 810.47 (M+1).
20. +] m/z = 3242.3, calcd: 3241.8. Preliminary circular dichroism studies of binding to the DNA fragment ds-(5'-AGGATTTTATGACGTTCG-3') suggest that hybrid 1 binds weakly, and apparently only via its the minor groove counterpart. Detailed studies will be reported in due course.