Impact of backbone N-amination on the stability of parallel beta-sheets

RESULTS 11) Backbone N-amination restores thermal stability in DS120 10 lowest energy states calculated from NMR distance-restrained simulated annealing 8) NMR-derived structures of wt Pbh reveal significant fraying at the termini and the Lys2 substitution site 4) SPPS of parallel -hairpin peptides featuring backbone amide substitutions * aX = N-amino Xaa, MeX = Nmethyl Xaa 2) Synthesis of N-amino dipeptide building blocks suitable for SPPS 9) Backbone substituted analogues of DS119: a miniprotein featuring a parallel sheet fold 10) N-Aminated DS119 analogues retain wild-type fold and thermal stability in 1M Gdn .HCl at 0.2 mg/mL in 20 mM sodium phosphate buffer (pH 7.3) 3) Synthesis of the resin-bound turn D-Pro-DADME motif 1) A parallel -hairpin (Pbh) model for investigating the impact of backbone amide substitution at 200 M in 10 mM aq.NaOAc (pH 3.8, 298 K) 6) H NMR chemical shift deviations define the folded core of amide-substituted -hairpin peptides 5) Backbone N-amino and N-methyl peptides retain a parallel -sheet CD signature 7) N-amination of core residues enhances folded population relative to parent and N-methyl peptides at 200 M in 10 mM aq.NaOAc (pH 3.8, 298 K) Derived from NMR CSD values of H of reporter residues in D 2 O (800 MHz, 100 mM AcOD, pH 3.8, 280 K)