Microwave-assisted guanidinylation in solid phase peptide synthesis: comparison of various reagents

Combinatorial Chemistry Online Volume 17, Issue 1, January 2015

“…The best results were obtained with N,N 0 -di-benzyloxycarbonyl-S-methylisothiourea and N,N 0 -di-(2-chlorobenzyloxycarbonyl)-S-methylisothiourea, as it was found that guanidinylation with reagents containing Boc groups was accompanied by side reactions [2].…”

Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis

“…Arginine (Arg, R) is the most basic natural amino acid [1][2][3] with the highest proton affinity (245.2 kcal/mol), while the second is histidine (231.2 kcal/mol) [4]. The pK a value of the guanidine group located in the side chain of Arg, measured in water, is lower (~12.5) than that of guanidine itself (~13.5) [2,3].…”

“…The Y-delocalized guanidine moiety is stabilized by resonance. There are six potential hydrogen bond donors, and it is highly soluble in an aqueous system [1,3]. Therefore, it is responsible for electrostatic and hydrogen bond interactions with anionic and polar molecules, especially in ligand-receptor or substrate-enzyme interactions [1,2].…”

“…There are six potential hydrogen bond donors, and it is highly soluble in an aqueous system [1,3]. Therefore, it is responsible for electrostatic and hydrogen bond interactions with anionic and polar molecules, especially in ligand-receptor or substrate-enzyme interactions [1,2]. Furthermore, Arg residue present in peptide chains participates in cation-π interactions, which are made up of the attractive force between cationic species and π-bonded systems (aromatic ring, allylic group) [3,5].…”

“…This discovery opened the possibility of obtaining guanidine derivatives from azides in a one-pot reaction. Witkowska et al [1] compared guanidinylation of peptides on resin with various reagents using microwaves. In this study, the results obtained for compound F were not so appealing, as the introduction of microwaves led to a significant amount of side products.…”