Structural highlights
Publication Abstract from PubMed
A synthetic antimicrobial peptide library based on the human autophagy 16 polypeptide has been developed. Designed acetylated peptides bearing lipids of different chain lengths, resulted in peptides with enhanced potency compared to the parent Atg16. A 21-residue fragment of Atg16 conjugated to 4-methylhexanoic acid (K30) emerged as the most potent antibacterial, with negligible hemolysis. Several studies, including microscopy, dye leakage and ITC were conducted to gain insight into the antibacterial mechanism of action of the peptide. Visual inspection using both SEM and TEM revealed the membranolytic effect of the peptide on bacterial cells. The selectivity of the peptide against bacterial cell membranes was also proven using dye leakage assays. ITC analysis revealed the exothermic nature of the binding interaction of the peptide to D8PG micelles. Three dimensional solution NMR structure of K30 in complex with dioctanoyl phosphatidylglycerol (D8PG) micelles revealed that the peptide adopts a helix-loop-helix structure in the presence of anionic membrane lipids mimicking bacterial membranes. Intermolecular NOEs between the peptide and lipid deciphered the location of the peptide in the bound state, which was subsequently supported by the paramagnetic relaxation enhancement (PRE) NMR experiment. Collectively, these results describe the structure function relationship of the peptide in the bacterial membrane.
Design, Synthesis, Antibacterial Potential and Structural Characterization of N-acylated Derivatives of Human Autophagy 16 Polypeptide.,Varnava KG, Mohid AS, Calligari P, Stella L, Reynisson J, Bhunia A, Sarojini V Bioconjug Chem. 2019 May 30. doi: 10.1021/acs.bioconjchem.9b00290. PMID:31145591[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Varnava KG, Mohid AS, Calligari P, Stella L, Reynisson J, Bhunia A, Sarojini V. Design, Synthesis, Antibacterial Potential and Structural Characterization of N-acylated Derivatives of Human Autophagy 16 Polypeptide. Bioconjug Chem. 2019 May 30. doi: 10.1021/acs.bioconjchem.9b00290. PMID:31145591 doi:https://dx.doi.org/10.1021/acs.bioconjchem.9b00290
