1. Syntheses of low-hemolytic antimicrobial gratisin peptides
Makoto Tamaki, et al. Bioorg Med Chem Lett. 2009 May 15;19(10):2856-9. doi: 10.1016/j.bmcl.2009.03.133. Epub 2009 Mar 28.
Antibiotic and hemolytic activities of gratisin (GR), cyclo(-Val(1)-Orn(2)-Leu(3)-d-Phe(4)-Pro(5)-d-Tyr(6)-)(2), and fifteen GR analogues, which have various d-amino acid residues in place of d-Tyr(6,6') residues, were examined. Among them, [d-Orn(6,6')]-GR, [d-Lys(6,6')]-GR and [d-Arg(6,6')]-GR showed the strong activity against both Gram-positive and Gram-negative bacteria. In addition, the antibiotics showed significantly reduced toxicity against human blood cells compared with gramicidin S, cyclo(-Val(1)-Orn(2)-Leu(3)-d-Phe(4)-Pro(5)-)(2).
2. A novel polycationic analogue of gratisin with antibiotic activity against both Gram-positive and Gram-negative bacteria
Makoto Tamaki, Manabu Kokuno, Yumiko Suzuki, Mitsuko Iwama, Mitsuno Shindo, Yoshiki Uchida J Antibiot (Tokyo). 2008 Jan;61(1):33-5. doi: 10.1038/ja.2008.106.
A novel polycationic analogue of gratisin, cyclo(-Val-Orn-Leu-D-Phe-Pro-D-Lys-)2, was designed and synthesized, which exhibited strong activity against all Gram-positive and Gram-negative bacteria tested. Its activity against Pseudomonas aeruginosa IFO 3080 was two times higher than gramicidin S.
3. The synthesis of an EDTA-like chelating peptidomimetic building block suitable for solid-phase peptide synthesis
Jan Spengler, Michael Barker, Constanze Schelhorn, Jesús García, Maria J Macias, Fernando Albericio Chem Commun (Camb). 2017 Feb 23;53(17):2634-2636. doi: 10.1039/c6cc10203d.
A novo trifunctional EDTA-like peptidomimetic amino acid is described. This unique building block, which is prepared in a straightforward manner from commercialized starting materials, contains three moieties: a hexadentate chelating unit similar to that present in EDTA, and amino and carboxylic groups, which facilitate its introduction into the backbone of peptides using conventional SPPS. As a proof of concept, this building block is introduced into a cyclic peptide inspired from the family of Gratisin analogues. The designed peptide contains the amino acid analogue in one of the turns, and chelates Ca2+ with nanomolar affinity at physiological pH.
