engleski

Synthesis of dipeptides containing photochemically reactive modifiyed tyrosine and evaluation of their dna binding

Quinone methides (QMs) are recative intermediates with a potential in the development of new leads for drugs owing to their reactivity with DNA, proteins and enzymes [1]. In particular, some anticancer antibiotics such as mitomycine base their action on metabolic formation of QMs and subsequent DNA cross-linking. Therefore, it is important to investigate different classes of simple QMs as potential anticancer agents. However, QM are reactive intermediates with short inherent lifetimes, so they have to be prepared in situ in the living cells. An excellent methodology for the generation of QMs in the biological systems are photochemical reactions of deamination or dehydration [2]. We have recently demonstrated that tyrosine derivatives can be modified into QM precursors and imbedded in proteins where they remain photochemically reactive [3]. Furthermore, it is known that photo-triggered DNA alkylation by QMs can be significantly enhanced by binding QM precursors to the DNA intercallators [4]. Here we present synthesis of dipeptides 1 and 2 that contain two unnatural amino acids, photochemically reactive tyrosine derivative and aminoacid bearing DNA intercalators- phenantridine [5] or pyrene [6]. Their non-colvalent and photo-triggered covalent DNA binding ability will be investigated.

quinone methides ; peptides ; DNA

nije evidentirano