Gerald Haaima
University of Copenhagen
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Featured researches published by Gerald Haaima.
Chemical Society Reviews | 1997
Peter E. Nielsen; Gerald Haaima
PNA (peptide nucleic acid) is a DNA mimic with a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units with the nucleobases attached to the glycine nitrogen via carbonyl methylene linkers. PNA was first described in 1991 and has since then attracted broad attention within the fields of bioorganic chemistry, medicinal chemistry, physical chemistry and molecular biology due to its chemical and physical properties, in particular with regard to efficient and sequence specific binding to both single stranded RNA and DNA as well as to double stranded DNA. The present review discusses the structural features that provide the DNA mimicking properties of PNA and gives an overview of structural backbone modifications of PNA.
Tetrahedron Letters | 1998
Ask Püschl; Stefano Sforza; Gerald Haaima; Otto Dahl; Peter E. Nielsen
Abstract The synthesis of 10 new T-PNA monomers derived from L-amino acids is presented. The monomers were incorporated into decameric PNA oligomers, and the hybridisation with RNA, DNA and PNA complements studied by thermal stability measurements.
European Journal of Organic Chemistry | 1999
Stefano Sforza; Gerald Haaima; Rosangela Marchelli; Peter E. Nielsen
Peptide Nucleic Acids (PNAs) are DNA mimics in which the deoxyribose phosphate backbone has been replaced by a pseudo-peptide skeleton composed of N-(2-aminoethyl)glycine units; they bind to complementary DNA strands with high affinity and selectivity. In order to study the effect of stereogenic centers within the backbone on PNA preorganization and DNA binding properties, chiral PNA decamers were synthesized which contained thymine monomers derived from L-Leu and D- or L-Lys inserted either at C-terminus and/or in the middle of an achiral PNA strand. PNAs containing three chiral thymine monomers derived from L-Leu, D- or L-Lys, L-Asp, or D-Glu were also synthesized. CD spectral analyses showed that a charged chiral monomer inserted in the middle of the strand is able to induce a strong preference in the helix handedness of a PNA-PNA duplex. The effect is increased by the presence of three chiral charged monomers. The L-Lys- and L-Asp-PNAs induced a preference for the left-handed and the D-Lys and D-Glu-PNAs for the right-handed conformation. As expected, the PNA-DNA duplexes are dominated by the DNA strand and thus are right-handed with both D- and L-PNAs. However, the D-PNAs, being inherently right-handed, lead to more stable PNA-DNA duplexes than the L-PNAs. The lysine-based PNAs form more stable complexes with the DNA at low ionic strength, due to the electrostatic interactions between the charged lysine side chain and DNA.
New Journal of Chemistry | 1998
Magdalena Eriksson; Leif Christensen; Jurgen G. Schmidt; Gerald Haaima; Leslie E. Orgel; Peter E. Nielsen
The stability of the PNA (peptide nucleic acid) thymine monomer ¿N-[2-(thymin-1-ylacetyl)]-N-(2-aminoaminoethyl)glycine¿ and those of various PNA oligomers (5-8-mers) have been measured at room temperature (20 degrees C) as a function of pH. The thymine monomer undergoes N-acyl transfer rearrangement with a half-life of 34 days at pH 11 as analyzed by 1H NMR; and two reactions, the N-acyl transfer and a sequential degradation, are found by HPLC analysis to occur at measurable rates for the oligomers at pH 9 or above. Dependent on the amino-terminal sequence, half-lives of 350 h to 163 days were found at pH 9. At pH 12 the half-lives ranged from 1.5 h to 21 days. The results are discussed in terms of PNA as a gene therapeutic drug as well as a possible prebiotic genetic material.
Bioorganic & Medicinal Chemistry Letters | 2002
Caspar Christensen; Anne B. Eldrup; Gerald Haaima; Peter E. Nielsen
A novel bicyclic mimic of protonated cytosine [1,8-naphthyridin-2,7-(1,8H)-dione, (K)] for Hoogsteen type triplex recognition of guanine has been designed for incorporation into peptide nucleic acids. Bis-PNA clamps with the K base incorporated in the Hoogsteen strand showed a significant stabilization of the triplexes at pH 7 as compared to similar triplexes with PNA oligomers containing either cytosine (6.7 degrees C per unit) or pseudoisocytosine (1.5 degrees C per unit). Cooperative stabilization was observed when the K units were placed in adjacent positions ( approximately 3 degrees C per unit).
Angewandte Chemie | 1996
Peter E. Nielsen; Gerald Haaima; Anders Lohse; Ole Buchardt
Biochemistry | 1998
Tommi Ratilainen; Anders Holmen; Eimer Tuite; Gerald Haaima; Leif Christensen; Peter E. Nielsen; Bengt Nordén
Nucleic Acids Research | 1997
Gerald Haaima; Henrik Hansen; Leif Christensen; Otto Dahl; Peter E. Nielsen
Journal of the American Chemical Society | 2002
Anne B. Eldrup; Caspar Christensen; Gerald Haaima; Peter E. Nielsen
European Journal of Organic Chemistry | 2001
Anne B. Eldrup; Bettina Bryde Nielsen; Gerald Haaima; Hanne B. Rasmussen; Jette S. Kastrup; Caspar Christensen; Peter E. Nielsen