Novel polyamide based nucleic acid analogs synthesis of oligomers and RNA-binding properties

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 9, 1997, Pages 1123-1126

  García Echeverría, Carlos ^a   Hüsken, Dieter ^a   Chiesi, Chantal Schmit ^a   Altmann, Karl Heinz ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEOTIDE DERIVATIVE; POLYAMIDE;

ARTICLE; DRUG SYNTHESIS; IN VITRO STUDY; REACTION ANALYSIS; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; RNA BINDING; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

EID: 0041757211     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00173-X     Document Type: Article

References (21)

1. Altmann, K.-H.; Schmit-Chiesi, C.; Garcia-Echeverría, C.; preceding paper in this issue.
2. For a comprehensive discussion of nucleic acid structures see: W. Saenger, "Principles of Nucleic Acid Structure", Springer, New York 1984.
3. The presence of α-methyl groups in carboxylic acid derivatives can impose significant conformational constraints. It is, e. g. a well known fact that the conformational space accessible to an alanyl residue in polypeptides is substantially smaller than for a glycyl residue, which in large part is a consequence of unfavorable interactions between the α-methyl group and the adjacent carbonyl oxygen. Likewise, the presence of α-methyl groups in poly(lactic acid) leads to greatly reduced flexibility of this polymer: Flory, P. J. "Statistical Mechanics of Chain Molecules". Interscience, New York 1969.
4. Rink, H. Tetrahedron Lett. 1987, 28, 3787 - 3790. Syntheses were carried out on a semi-automated peptide synthesizer using 140 - 190 mg of resin.
5. Knorr, R.; Trzeciak, A.; Bannwarth,. W.; Gillesen, D. Tetrahedron Lett. 1989, 30, 1927 - 1930.
6. Efficient incorporation of the N-terminal lysine residue in general required double-coupling.
7. Atherton, E.; Sheppard, R. C. In Solid Phase Peptide Synthesis: A Practical Approach: IRL Press, Oxford 1989.
8. 3 containing 5% acetic acid and 2.5% N-methyl-morpholine: Kates, S. A.; Daniels, S. B.; Albericio, F. Anal. Biochem. 1993, 212, 303 - 310.
9. 3 containing 5% acetic acid and 2.5% N-methyl-morpholine: Kates, S. A.; Daniels, S. B.; Albericio, F. Anal. Biochem. 1993, 212, 303 - 310.
10. Tam, J. P; Heath, W. F.; Merrifield, R. B. J. Am. Chem. Soc. 1986, 108, 5242 - 5251.
11. Experimentally determined molecular masses were within 0.1% of the expected values (positive or negative-ion mode): A, 3787.1 (calc. 3787.8); B, 3996.7 (calc. 3996.2); C, 3925.9 (calc. 3926.1); and D, 3926.9 (calc. 3926.1).
12. The terms "antiparallel" and "parallel" RNA complements refer to the Watson-Crick alignment of oligomers A - D in the N → C direction with the RNA in the 3' → 5' ("antiparallel") and 5' → 3' ("parallel") direction.
13. m measurements cf.: Lesnik, E. A.; Guinosso, C. J.; Kawasaki, A. M.; Sasmor, H.; Zounes, M.; Cummins, L. L.; Ecker, D. J.; Cook, P. D.; Freier, S. M. Biochemistry 1993, 32, 7832 - 7838.
14. m measurements cf.: Lesnik, E. A.; Guinosso, C. J.; Kawasaki, A. M.; Sasmor, H.; Zounes, M.; Cummins, L. L.; Ecker, D. J.; Cook, P. D.; Freier, S. M. Biochemistry 1993, 32, 7832 - 7838.
15. 5] (Tm-values of 52° and 48°, respectively).
16. 5], respectively).
17. Likewise, no cooperative melting was observed upon heating a solution of single-stranded A.
18. For recent reviews cf.: a. De Mesmaeker, A.; Häner, R.; Martin, P.; Moser, H. E. Acc. Chem. Res. 1995, 28, 366 - 374.
19. b. De Mesmaeker, A.; Altmann, K.-H.; Waldner, A.; Wendeborn, S. Curr. Opinion Struct. Biol. 1995, 5, 343 - 355.
20. m = 21.7° vs. ∼ 6.8°).
21. We have not determined the stoichiometry of the complexes of A and C with complementary RNA. As all melting curves were indicative of a single cooperative transition and no hysterisis was observed upon cooling, we assume that A as well as C bind to RNA with 1/1 stoichiometry. In contrast, the binding of an isosequential PNA to RNA is characterized by strong hysterisis in UV melting experiments (D. Hüsken, K.-H. Altmann, unpublished data). Nevertheless, we cannot exclude the possibility that A and/or C form 2/1 complexes with complementary RNA. However, in either case the data presented in this work demonstrate that binding occurs in a defined and sequence specific fashion.