Structural determinants of spermidine–DNA interactions

Abstract

Abstract Twelve different analogs of spermidine (SPD) and SPD itself were compared for their ability to modulate two conformational transitions of DNA; the B‐to‐Z conformational transition of poly(dG‐me 5 dC) and the thermal melting transition of calf thymus DNA. The analogs consisted of five N‐ethyl‐SPD derivatives [N 1 ‐ethyl‐SPD, N 4 ‐ethyl‐SPD, N 8 ‐ethyl‐SPD, N 1 ,N 8 ‐bis(ethyl)SPD and N 1 ,N 4 ,N 8 ‐tri(ethyl)SPD], which differed in the number and/or position of the ethyl substitution (the alkyl series); three N‐acetyl‐SPD derivatives (N 1 ‐acetyl‐SPD, N 4 ‐acetyl‐SPD, and N 8 ‐acetyl‐SPD), which were comparable to the N‐ethyl‐SPD derivatives but not protonated at the substituted amine (the acyl series); three aliphatic analogs [nor‐SPD, homo‐SPD, and N 1 ,N 9 ‐bis(ethyl)homo‐SPD], which differed in the interamine carbon chain length (homolog series), and 1,8‐diaminooctane, which was comparable in overall chain length to SPD but lacked a central nitrogen. By comparing the relative abilities of the various analogs and SPD to modulate DNA structural transitions, it is possible to gain insight into the relative significance of the number and location of protonated amines (acyl series), the number and location of steric groups (alkyl series), aliphatic chain length (homolog series), and the central amine (1,8‐diaminooctane) as determinants of SPD–DNA interactions. The B‐to‐Z conformational transition was facilitated to a midpoint by 2.4 μ M SPD under conditions of low (i.e., 11 m M Na + ) ionic strength. The phenomenon was affected most significantly by the number of protonated amines followed in rank order by location of the protonated amines, number of steric groups (bulk), steric group location, and aliphatic chain length. Stabilization of DNA to thermal melting was also most affected by the number of protonated amines followed by aliphatic chain length, number of steric groups, and location of protonated amines. In general, substitutions at the central (N 4 ) amine of SPD exerted a significant influence on the B‐to‐Z transition but not on thermal melting.