Poster Presentation 12th Australian Peptide Conference 2017

Synthesis and biological evaluation of Teixobactin analogues (#96)

Yahya E. Jad 1 , Shimaa A. H. Abdel Monaim 1 , Estelle J. Ramchuran 1 , Sikabwe Noki 1 , Gerardo A. Acosta 2 3 , Ayman El-Faham 4 5 , Beatriz G. de la Torre 1 6 , Fernando Albericio 1 2 3 4 7
  1. School of Health Sciences, University of KwaZulu-Natal, Durban, KWAZULU-NATAL, South Africa
  2. Department of Organic chemistry, University of Barcelona, Barcelona, Spain
  3. CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona, Spain
  4. Department of Chemistry-College of Science , King Saud University, Riyadh, Saudi Arabia
  5. Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
  6. School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa
  7. School of Chemistry and Physics, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa

The discovery of teixobactin in January 2015 has attracted the attention of the scientific society because of dramatic increase of antibiotic resistance. It showed highly potent activities against Gram-positive bacteria, including drug-resistant strains, and Mycobacterium tuberculosis. It is a 11-mer cyclodepsipeptide with a four residue in the macrocycle and seven in the tail, and five non-proteinoginic amino acids namely; L-allo-enduracididine, D-Thr, D-allo-Ile, D-Gln, and N-Me-D-Phe. The total synthesis of teixobactin has been reported by Payne’s group.

We have reported in December 2015 the synthesis of Arg10-analogue by substituting of L-allo-End by L-Arg. Arg10-Teixobactin showed activities in the same trend as teixobactin, i.e. potent activities against Gram-positive bacteria and less active against Gram-negative bacteria. Later, our group and groups of Singh, Nowick and Fang have independently reported several teixobactin analogues. Herein, we are going to present SAR studies by investigating of changing of N-terminal, the balance of hydrophilic and hydrophobic residues (Lys scan), and the increasing of the positive charges in Arg10-teixbactin (multi-Lys incorporation).

  1. 1- S. A. H. Abdel Monaim, Y. E. Jad, E. J. Ramchuran, A. El-Faham, T. Govender, H. G. Kruger, B. G. de la Torre, F. Albericio, ACS Omega 2016, 1, 1262−1265 and references cited therein.