1620146-29-3Relevant articles and documents
N-Hydroxy peptides: solid-phase synthesis and ?-sheet propensity
Sarnowski, Matthew P.,Del Valle, Juan R.
supporting information, p. 3690 - 3696 (2020/06/03)
Peptide backbone amide substitution can dramatically alter the conformational and physiochemical properties of native sequences. Although uncommon relative toN-alkyl substituents, peptides harboring main-chainN-hydroxy groups exhibit unique conformational preferences and biological activities. Here, we describe a versatile method to prepareN-hydroxy peptide on solid support and evaluate the impact of backboneN-hydroxylation on secondary structure stability. Based on previous work demonstrating the ?-sheet-stabilizing effect of a-hydrazino acids, we carried out an analogous study withN-hydroxy-a-amino acids using a model ?-hairpin fold. In contrast toN-methyl substituents, backboneN-hydroxy groups are accommodated in the ?-strand region of the hairpin without energetic penalty. An enhancement in ?-hairpin stability was observed for a di-N-hydroxylated variant. Our results facilitate access to this class of peptide derivatives and inform the use of backboneN-hydroxylation as a tool in the design of constrained peptidomimetics.
