International Journal of Molecular Sciences Article Synthesis of Fmoc-Triazine Amino Acids and Its Application in the Synthesis of Short Antibacterial Peptidomimetics 1, 2 1 1,3, Pethaiah Gunasekaran y , Eun Young Kim , Jian Lee , Eun Kyoung Ryu y, Song Yub Shin 2,4 and Jeong Kyu Bang 1,3,* 1 Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang 28119, Korea;
[email protected] (P.G.);
[email protected] (J.L.);
[email protected] (E.K.R.) 2 Department of Medical Science, Graduate School, Chosun University, Gwangju 61452, Korea;
[email protected] (E.Y.K.);
[email protected] (S.Y.S.) 3 Department of Bio-analytical Science, University of Science & Technology, Daejeon 34113, Korea 4 Department of Cellular and Molecular Medicine, School of Medicine, Chosun University, Gwangju 61452, Korea * Correspondence:
[email protected]; Tel.: +82-43-240-5023 These authors contributed equally to this work. y Received: 22 April 2020; Accepted: 18 May 2020; Published: 20 May 2020 Abstract: To combat the escalating rise of antibacterial resistance, the development of antimicrobial peptides (AMPs) with a unique mode of action is considered an attractive strategy. However, proteolytic degradation of AMPs remains the greatest challenge in their transformation into therapeutics. Herein, we synthesized Fmoc-triazine amino acids that differ from each other by anchoring either cationic or hydrophobic residues. These unnatural amino acids were adopted for solid-phase peptide synthesis (SPPS) to synthesize a series of amphipathic antimicrobial peptidomimetics. From the antimicrobial screening, we found that the trimer, BJK-4 is the most potent short antimicrobial peptidomimetic without showing hemolytic activity and it displayed enhanced proteolytic stability.