9IO3

D-Amino Acid Substituted Antimicrobial Peptides Derived from Tilapia piscidin 4

Summary for 9IO3

• Entry DOI: 10.2210/pdb9io3/pdb
• NMR Information: BMRB: 36684
• Descriptor: Tilapia piscidin 4 alpha (1 entity in total)
• Functional Keywords: structure from cyana 3.98.15, antimicrobial protein
• Biological source: Oreochromis niloticus
• Total number of polymer chains: 1
• Total formula weight: 3089.95

Authors

Huang, Y.P.,Chang, C.F. (deposition date: 2024-07-08, release date: 2025-07-16, Last modification date: 2026-01-28)

Primary citation

Hsu, P.H.,Hazam, P.K.,Huang, Y.P.,Yeh, J.C.,Chen, Y.R.,Li, C.C.,Chang, C.F.,Liou, J.W.,Chen, J.Y.
Optimization of sequence and chiral content enhances therapeutic potential of tilapia piscidin peptides.
Eur.J.Med.Chem., 265:116083-116083, 2024

PubMed Abstract: Because antimicrobial peptides (AMPs) often exhibit broad-spectrum bactericidal potency, we sought to develop peptide-based antimicrobials for potential clinical use against drug-resistant pathogens. To accomplish this goal, we first optimized the amino acid sequence of a broad-spectrum AMP known as Tilapia Piscidin 4 (TP4). Then, we used the optimized sequence to create a pair of heterochiral variants (TP4-α and TP4-β) with different percentages of D-enantiomers, as poly-L peptides often exhibit poor pharmacokinetic profiles. The conformations of the peptide pair exhibited inverted chirality according to CD and NMR spectroscopic analyses. Both heterochiral peptides displayed enhanced stability and low hemolysis activities. Irrespective of their different d-enantiomer contents, both heterochiral peptides exhibited bactericidal activities in the presence of human serum or physiological enzymes. However, the peptide with higher d-amino acid content (TP4-β) caused better bacterial clearance when tested in mice infected with NDM-1 K. pneumoniae. In addition, we observed a relatively higher hydrogen bonding affinity in a simulation of the interaction between TP4-β and a model bacterial membrane. In sum, our results demonstrate that the current design strategy may be applicable for development of new molecules with enhanced stability and in vivo antimicrobial activity.

PubMed: 38150960
DOI: 10.1016/j.ejmech.2023.116083

Experimental method

SOLUTION NMR