α-Helical Peptide Containing N,N-Dimethyl Lysine Residues Displays Low-Nanomolar and Highly Specific Binding to RRE RNA

Effects of Asymmetric Arginine Dimethylation on RNA‐Binding Peptides

“…In general, the a-helical contents of Rev proteins are known to increase in the presence of RRE as a result of an induced-fit mechanism. [17,18] Unlike the generally observed reduction of a helicity that is brought about by lysine methylation, [11] the a-helical content of Rev peptides vary according to the position of Arg methylation. Furthermore, a correlation appears to exist between the percentage a helicity and binding affinity (K a , nm) of the Arg methylated Rev peptides as demonstrated by the plot of data from Table 1 that is shown in Figure 2; this correlates with the relationship given by Frankel et al [18,19] Although R35 is at the top of the directly proportional correlation and the reverse sequence reference peptide, Rev , is at the bottom, many exceptions to the correlation exist.…”

“…It should be noted that positive effects associated with the interaction switch has not been A C H T U N G T R E N N U N G observed in biological system, per se. [11] Experimental Section Syntheses of peptides: A library of peptides was synthesized by using the standard Fmoc solid-phase protocol. The N a -Fmoc-N w ,N w -asymmetric dimethylarginine hydrochloride salt was used for asymmetric dimethylarginine synthesis.…”

“…The well known RBP, Rev, is a key peptide in HIV propagation. When A C H T U N G T R E N N U N G unspliced or partially spliced viral RNA is imported into the nucleus, Rev binds to the Rev responsive element (RRE) in the RNA of HIV-1 and increases gene transcription.[10] Furthermore, the Rev peptide has a-helical structures, which provide opportunities to explore the effects of methylation on conformational rigidity.The effects of methylation might depend on the position [11] and number of asymmetric dimethylated Arg residues, which result from the operation of a major methylation mode. [1,12] A recent report suggested that Rev is a substrate for asymmetric dimethylation.…”

HIV-1 drug discovery: targeting folded RNA structures with branched peptides

“…A compound containing two N-methylated lysines (K*), LKK*LLKLLK*KLLKLKG, had a K d of 9.1 nM and showed a fivefold selectivity for RRE against a mixture of tRNAs as well as TAR RNA. 50 Further modifications of calmodulin included the introduction of acridine (K**) at the epsilon amine of lysine as an intercalator, and mono- and bis-acridinylated peptides were examined as RRE binders. It was found that the position of the acridinyl lysine affected the binding affinity of the peptides, with mono acridinylated peptides 3 , 4 , and 5 demonstrating better binding affinities towards RNA but with little selectivity.…”

The charge ratio between O and N on amide bonds: A new approach to the mobile proton model

“…This model professes that the fragmentation of most protonated peptides is charge-directed and the proton can move from the more basic sites to the amide bonds (the main cleavage sites) through external energy input, producing the b n and y n ions, and so on [19][20][21][22][23]. Fragmentation efficiency curves [17,23] or quantum chemistry calculations [24][25][26] were employed to support this theory. Fragmentation efficiency curves are a way of comparing the ease of peptide cleavage and the results show some factors impacting fragmentation process of protonated peptides, such as the number of added protons, peptide composition, gas-phase basicity, and chemical modification [17,23].…”