Similar rates for platination of hairpin loops and single-stranded DNA

Abstract

The presence of ribonucleic acid hairpin structures is important for proper processing of the genetic information in living cells. Recent studies indicate that interactions between platinum based anticancer active metal complexes and hairpin motifs result in a change of their three-dimensional structure combined with a decrease of the melting temperature. We here report a study of the reaction between two platinum complexes, cis-ϩ II, and a series of short DNA hairpins which all exhibit a documented preference for adduct formation with donor groups located in the loop region; d(CGCGTTXTTCGCG), where X = G-N7, p(S), s6 I or s4 U. The binding kinetics of adduct formation with the hairpins have been compared with that of binding to similar size single-stranded DNA; d(T 6 XT 6 ), where X = G, p(S), s6 I or s4 U. The overall picture reveals rather similar reactivity of the platinum complexes towards these two DNA secondary structures. However, the smaller complex I exhibits a tendency for preferential interaction with the hairpins, whereas the more bulky complex II shows a higher reactivity towards the single-stranded structures.

27 Mechanisms of reactions in solution

“…Investigation of the reactivity of the two Pt(II) complexes, cis-[PtCl(NH 3 ) 2 (H 2 O)] 1 and cis-[PtCl(NH 3 )(c-NH 2 C 6 H 11 )(H 2 O)] 1 with hairpin DNA structures shows that the former has a preference for interaction with hairpin structures and the latter with single strand structures. 165 The effect on the rate of hydrolysis of a variety mono-and poly-nuclear platinum complexes with anticancer properties has been found to be influenced by the nature of the DNA template present during the hydrolysis. 166 The enhancement of rate is more marked for single-stranded template DNA than for the double-stranded variety and more rapid for poly-nuclear complexes than for mono-nuclear.…”

Σύμπλοκες ενώσεις του Zn(II) με πυριδυλοξίμες

“…Ηλεκτροστατικές αλληλεπιδράσεις και δέσμευση στις αύλακες [179][180][181][182][183][184][185][186][187] Οι μη ομοιοπολικές αλληλεπιδράσεις με τα νουκλεϊκά οξέα είναι ιδιαίτερα σημαντικές, κυρίως, γιατί συνεισφέρουν στη μοριακή αναγνώρισή τους. Τα αποδιοργάνωση στην περιοχή τους της κανονικής στοίβαξης των βάσεων, γεγονός το οποίο προκαλεί μια τοπική στρέβλωση (kink) στη δομή του μορίου DNA.…”

“…Τα αποδιοργάνωση στην περιοχή τους της κανονικής στοίβαξης των βάσεων, γεγονός το οποίο προκαλεί μια τοπική στρέβλωση (kink) στη δομή του μορίου DNA. Η παραμόρφωση αυτή φαίνεται ότι καθιστά το μόριο του DNA μη λειτουργικό, γεγονός που οδηγεί στο θάνατο του κυττάρου [179][180][181][182][183][184][185][186].…”