Recent Studies on Gramicidin S Analog Structure and Antimicrobial Activity

Sudip Pal, Uttam Ghosh, Ravi Sankar Ampapathi, and Tushar Kanti Chakraborty

Dedicated to Prof. S. Chandrasekaran on the occasion of his 70th birthday.

Abstract Gramicidin S, the most notable example of cationic antimicrobial peptides (CAPs), has remained in the forefront of worldwide research for development of new antibiotics for over seven decades now. Hundreds of papers have been published over the years on this molecule and its numerous analogs, delineating their structures and biological activities with an aim to achieve selective antimicrobial activities with reduced cytotoxicity for potential therapeutic applications. The present review attempts to capture the essence of some of the recent studies with the aims to chronicle the journey traversed by this fascinating molecule so far and to decipher what is needed for future success.

Keywords Antibiotics • Antimicrobial activities • Cationic antimicrobial peptides • Gramicidin S

Contents

• 1 Introduction................................................................................. 160
• 1.1 General................................................................................ 160
• 1.2 Structure and Conformation .......................................................... 161
• 1.3 Mechanism of Action................................................................. 161
• 1.4 Effect of Cholesterol.................................................................. 163
• 1.5 Activity................................................................................ 163
• 2 Modifications and Consequences........................................................... 164

S. Pal and R.S. Ampapathi

CSIR-Central Drug Research Institute, Lucknow 226031, India U. Ghosh and T.K. Chakraborty (*)

Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India e-mail: This email address is being protected from spam bots, you need Javascript enabled to view it

• 2.1 Ring Size.............................................................................. 165
• 2.2 Effect of N-Methylation.............................................................. 174
• 2.3 Exchange of Amino Acid............................................................. 178
• 2.4 SAA-Based Analogs.................................................................. 189
• 3 GS Dimers and Polymers................................................................... 195
• 4 GS as Catalyst............................................................................... 197
• 5 Synergistic Effect ........................................................................... 198
• 6 Conclusions.................................................................................. 198

References ....................................................................................... 199