A mixed chirality α-helix in a stapled bicyclic and a linear antimicrobial peptide revealed by X-ray crystallography

Abstract

The peptide α-helix is right-handed when containing amino acids with L-chirality, and left-handed with D-chirality, however mixed chirality peptides generally do not form α-helices unless the non-natural residue amino-isobutyric acid...

An intrinsically disordered antimicrobial peptide dendrimer from stereorandomized virtual screening

“…CD spectra of L- X18 (and its enantiomer D- X18 ) showed a transition from an unordered conformation in water to a more α-helical conformation in the presence of 20% v/v trifluoroethanol (TFE) as folding inducer or 5 mM n- dodecylphosphocholine (DPC) as a micelle-forming additive mimicking the membrane environment ( Figures 4 A, 4B, and S31 ). 13 , 53 , 54 L- X22 (and its D-enantiomer) was also disordered in water and partially α-helical with TFE. However, its CD trace in the presence of DPC has a shape intermediate between the unordered trace in water and the α-helical trace with TFE, indicating a less extensive α-helical folding with DPC micelles ( Figure 4 B).…”

“…In our own efforts to develop antibacterial agents, 10 , 11 , 12 , 13 we recently discovered that AMP dendrimers (AMPDs; e.g. L- G3KL ; Figure 1 ) 14 , 15 are potent antibacterial agents acting by a membrane disruptive mechanism similar to AMPs, 16 as do various cationic amphiphiles such as cyclic peptides, 17 polymers, 18 peptidomimetics, 19 foldamers, 20 and dendrimers.…”

Machine Learning Guided Discovery of Non‐Hemolytic Membrane Disruptive Anticancer Peptides

“…Considering that many ACPs are also antibacterial, [46] we determined minimum inhibitory concentrations (MIC) on Pseudomonas aeruginosa (PAO1) and Acinetobacter baumannii, two Gram-negative bacteria which are often sensitive to membrane disruptive AMPs. [15,47,48] Indeed, all but one of the synthesized peptides from the first series showed substantial antibacterial Toxicity [b] IC 50 /μM Hemolysis [c] HC 50 /μM MIC [d] μg/mL CD [e] % Vesicle leakage [f] nr.…”

Current synthetic chemistry towards cyclic antimicrobial peptides

“…However, its corresponding linear peptide displayed comparably strong antibacterial activity and high serum stability, but reduced hemolysis. 50…”

“…The bicyclic peptide showed improved antibacterial activity and protease stability, but increased hemolytic toxicity. However, its corresponding linear peptide displayed comparably strong antibacterial activity and high serum stability, but reduced hemolysis 50 …”