Application of Dmb-Dipeptides in the Fmoc SPPS of Difficult and Aspartimide-Prone Sequences

摘要: Mutter’s pseudoproline dipeptides and Sheppard’s Hmb derivatives are powerful tools for enhancing synthetic efficiency in Fmoc SPPS. They work by exploiting the natural propensity of N-alkyl amino acids to disrupt formation secondary structures during peptide assembly. Their use results better more predictable acylation deprotection kinetics, enhanced reaction rates, improved yields crude products. However, these approaches have certain limitations: can only be used sequences containing serine or threonine, coupling acid following residue extremely difficult. To alleviate some shortcomings, we prepared a range Fmoc-Aaa-(Dmb)Gly-OH tested their efficacy synthesis number challenging hydrophobic peptides. We also compared N-Dmb against N-Hmb backbone protection preventing aspartimide SPPS peptides Asp-Gly sequence.