Alanine scan reveals modifiable residues in teixobactin.

An alanine scan of Lys10-teixobactin reveals that a cationic residue at position 10 is not necessary for antibiotic activity and that position 3 tolerates substitution without loss of activity. An unexpected correlation between poor aqueous solubility and better antibiotic activity of the teixobactin analogues is observed.

[1]  Xuechen Li,et al.  Synthesis and structure-activity relationship of teixobactin analogues via convergent Ser ligation. , 2017, Bioorganic & medicinal chemistry.

[2]  F. Albericio,et al.  Converting Teixobactin into a Cationic Antimicrobial Peptide (AMP). , 2017, Journal of medicinal chemistry.

[3]  J. Ziller,et al.  X-ray crystallographic structure of a teixobactin analogue reveals key interactions of the teixobactin pharmacophore. , 2017, Chemical communications.

[4]  Z. Pan,et al.  Synthesis and structure–activity relationship studies of teixobactin analogues , 2017 .

[5]  Yahya E. Jad,et al.  Lysine Scanning of Arg10–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues , 2016, ACS omega.

[6]  Ebrahim H Ghazvini Zadeh,et al.  Total synthesis of teixobactin , 2016, Nature Communications.

[7]  Yahya E. Jad,et al.  Re-evaluation of the N-terminal substitution and the D-residues of teixobactin , 2016 .

[8]  Kevin H. Chen,et al.  Elucidation of the Teixobactin Pharmacophore. , 2016, ACS chemical biology.

[9]  A. Madder,et al.  Efficient total syntheses and biological activities of two teixobactin analogues. , 2016, Chemical communications.

[10]  Yahya E. Jad,et al.  Synthesis and Biological Evaluation of a Teixobactin Analogue. , 2015, Organic letters.

[11]  K. Lewis,et al.  A new antibiotic kills pathogens without detectable resistance , 2015, Nature.

[12]  S. Gellman,et al.  Hydrophile scanning as a complement to alanine scanning for exploring and manipulating protein–protein recognition: Application to the Bim BH3 domain , 2008, Protein science : a publication of the Protein Society.