109012-46-6

Upstream product

• 79-37-8 oxalyl dichloride 
• 75-09-2 dichloromethane 
• 109012-24-0 1-methyl-4-nitro-1H-imidazole-2-carboxylic acid 
• 109012-23-9 ethyl 1-methyl-4-nitroimidazole-2-carboxylate 
• 30148-21-1 ethyl 1-methyl-1H-imidazole-2-carboxylate 

Downstream Products

• 1006381-83-4 C₁₂H₁₁N₃O₄ 

Relevant academic research and scientific papers

Design, synthesis, and DNA binding characteristics of a group of orthogonally positioned diamino, N-formamido, pyrrole- and imidazole-containing polyamides

Orthogonally positioned diamino/dicationic polyamides (PAs) have good water solubility and enhanced binding affinity, whilst retaining DNA minor groove and sequence specificity compared to their monoamino/monocationic counterparts. The synthesis and DNA binding properties of the following diamino PAs: f-IPI (3a), f-IPP (4), f-PIP (5), and f-PPP (6) are described. P denotes the site where a 1-propylamino group is attached to the N1-position of the heterocycle. Binding of the diamino PAs to DNA was assessed by DNase I footprinting, thermal denaturation, circular dichroism titration, biosensor surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) studies. According to SPR studies, f-IPI (3a) bound more strongly (Keq = 2.4 × 10 8 M-1) and with comparable sequence selectivity to its cognate sequence 5′-ACGCGT-3′ when compared to its monoamino analog f-IPI (1). The binding of f-IPI (3a) to 5′-ACGCGT-3′ via the stacked dimer motif was balanced between enthalpy and entropy, and that was quite different from the enthalpy-driven binding of its monoamino parent f-IPI (1). f-IPP (4) also bound more strongly to its cognate sequence 5′-ATGCAT- 3′ (Keq = 7.4 × 106 M-1) via the side-by-side stacked motif than its monoamino analog f-IPP (2a). Although f-PPP (6) bound via a 1:1 motif, it bound strongly to its cognate sequence 5′-AAATTT-3′ (Keq = 4.8 × 107 M -1), 15-times higher than the binding of its monoamino analog f-PPP (2c), albeit f-PPP bound via the stacked motif. Finally, f-PIP (5) bound to its target sequence 5′-ATCGAT-3′ as a stacked dimer and it has the lowest affinity among the diamino PAs tested (Keq 5 M-1). This was about two times lower in affinity than the binding of its monoamino analog f-PIP (2b). The results further demonstrated that the 'core rules' of DNA recognition by monoamino PAs also apply to their diamino analogs. Specifically, PAs that contain a stacked IP core structure bind most strongly (highest binding constants) to their cognate GC doublet, followed by the binding of PAs with a stacked PP structure to two degenerate AT base pairs, and finally the binding of PAs with a PI core to their cognate CG doublet.

Recognition in the minor groove of DNA at 5′-(A,T)GCGC(A,T)-3′ by a four ring tripeptide dimer. Reversal of the specificity of the natural product distamycin

The tripeptide ImPImP containing alternating imidazole and pyrrole carboxamides specifically binds the designated six base pair site 5′-d(A,T)GCGC(A,T)-3′ in the minor groove of DNA. Quantitative footprint titration experiments demonstrate that ImPImP binds the sites 5′-AGCGCT-3′ and 5′-TGCGCA-3′ with apparent first order binding affinities of 3.8 × 105 M-1 and 3.6 × 105 M-1, respectively (25 mM tris acetate, 10 mM NaCl, pH 7.0 and 22 °C). Affinity cleaving experiments with ImPImP-EDTA·Fe reveals equal cleavage on both sides of the 5′-(A,T)-GCGC(A,T)-3′ site, consistent with a side-by-side antiparallel arrangement of the four ring peptides in the minor groove. This reversal of specificity of the natural product distamycin which prefers to bind pure A,T sequences underscores the utility of 2:1 peptide - DNA models for the design of ligands for sequence-specific recognition in the minor groove of DNA. By extending these peptides to four ring systems, a new lower limit of six base pair binding by 2:1 peptide - DNA complexes has been defined.

Design, synthesis and DNA binding properties of orthogonally positioned diamino containing polyamide f-IPI

An orthogonally positioned diamino/dicationic polyamide f-IPI 2 was synthesized. It has enhanced binding affinity, and it showed comparable sequence specificity to its monoamino/monocationic counterpart f-IPI 1. Results from CD and DNase I footprinting studies confirmed the minor groove binding and selectivity of polyamides 1 and 2 for the cognate sequence 5′-ACGCGT-3′ SPR studies provided their binding constants: 2.4×108M-1 for diamino 2, which is ～4 times higher than 5.4×107M-1 for its monoamino analogue 1.

Solution phase synthesis of imidazole- and pyrrole-containing hairpin polyamides

Hairpin imidazole (I)- and pyrrole (P)-containing polyamide analogs of distamycin that bind at specific sequences in the minor groove of DNA are potentially useful gene control agents. There is a pressing need for efficient syntheses of such polyamides. The syntheses of four specific hexaheterocyclic hairpin polyamides (PIP- γ -PPP 1, PIP- γ -PII 2, PIP- γ -III 3, and PIP- γ -IPI 4, γ represents 4-aminobutyrate) using a solution phase approach are reported.

Imidazole-containing compositions and methods of use thereof analogs of distamycin

The present invention relates to oligopeptide derivatives that are conjugated to DNA alkylating agents, having the formula STR1 wherein m is 0 to 4; n is 2 to 4; each R1 is the same or different and is hydrogen or C1 -C4 a

Synthesis of Novel Imidazole-Containing DNA Minor Groove Binding Oligopeptides Related to the Antiviral Antibiotic Netropsin

Analysis of the structural and stereochemical requirements for the strict DNA base sequence recognition of (AT)4 and (AT)5 respectively for the oligopeptide minor groove binding agents netropsin and distamycin leads to proposals for the rational structure