Site-Specific Photomodification of DNA by Porphyrin−Oligonucleotide Conjugates Synthesized via a Solid Phase H-Phosphonate Approach

Abstract

meso-Tris(4-pyridyl)[[(omega-hydroxyhexamethylene)carbamoyl]phenyl ] porphyrin was converted to its H-phosphonate derivative and conjugated using solid phase synthesis with the 5'-hydroxyl group of deoxyribonucleotides d(TCTTCCCA) and d(T)12. These conjugates were transformed into their (N-methylpyridiniumyl)porphyrin analogs in the reaction with methyl iodide. A 532 nm laser beam was utilized to photoactivate both types of the conjugates in the presence of the target 22-mer and 16-mer oligonucleotides. Photoactivation of porphyrin-oligonucleotide conjugates resulted in site-specific DNA modification characterized by a main reaction site size of approximately 5 bases.

Significantly Enhanced DNA Thermal Stability Resulting from Porphyrin H‐Aggregate Formation in the Minor Groove of the Duplex

“…[17,18] This provides structures that have porphyrin residues as 3'-or 5'-molecular caps, [12,[18][19][20] thus introducing them instead of a nucleobase in the middle of the helix [17] or as a label in the minor [10,16] and major [6][7][8] grooves. Recently, the synthesis of a DNA containing eleven meso-functionalized porphyrins attached to 5-ethynyl-2'-deoxyuridines was carried out from the corresponding phosphoramidites; however, this showed a significant thermal destabilization of the resulting duplex.…”

“…[7] Due to their chemical nature, the stability of porphyrin phosphoramidites as DNA building blocks is usually limited [10,11] and depends on the structure of the molecule. H-phosphonate porphyrin analogues were also employed in DNA synthesis; [10,19] however, coupling yields are usually not satisfactory for their multiple incorporation. In this regard, a postsynthetic modification of DNA, in which a functional group of the label reacts with the complementary functional group on the DNA, is a more versatile approach compared to the time-consuming preparation of phosphoramidites.…”

Current Developments in Using MESO-(TETRA) Substituted Porphyrins for PDT

“…103 A typical example is the synthesis of water-soluble porphyrin-oligonucleotide (ODN) conjugates 140a-c by Mammana et al (Fig. 29).…”

Synthesis of β‐Pyrrolic‐Modified Porphyrins and Their Incorporation into DNA

“…[3] The site-specific covalent attachment of porphyrin moieties to DNA has been achieved by using a variety of methodologies including the modification of nucleobases, [4][5][6][7][8][9] ribofuranose residues, [10][11][12][13][14][15] the phosphate backbone [16,17] and acyclic linkers. [18,19] Porphyrin moieties have been introduced as 3'-or 5'-molecular caps, [13,[19][20][21] as a nucleobase substituent in the middle of the helix [18] or as a label in the minor [11,17,22] and major [5][6][7][8][9] grooves. Several tethers have been used for the covalent attachment of porphyrins including maleimidothiols, [8,17] amides, [11][12][13]15] phosphates [16] and alkynes.…”