1620146-29-3Relevant academic research and scientific papers
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.
Comparison of backbone modification in protein β-sheets by α→γ residue replacement and α-residue methylation
Lengyel, George A.,Reinert, Zachary E.,Griffith, Brian D.,Horne, W. Seth
, p. 5375 - 5381 (2014/07/21)
The mimicry of protein tertiary structure by oligomers with unnatural backbones is a significant contemporary research challenge. Among common elements of secondary structure found in natural proteins, sheets have proven the most difficult to address. Here, we report the systematic comparison of different strategies for peptide backbone modification in β-sheets with the goal of identifying the best method for replacing a multi-stranded sheet in a protein tertiary fold. The most effective sheet modifications examined led to native-like tertiary folding behavior with a thermodynamic folded stability comparable to the prototype protein on which the modified backbones are based. This journal is the Partner Organisations 2014.
