Karishma Biswas, Humaira Ilyas, Aritreyee Datta and Anirban Bhunia* Pages 1387 - 1404 ( 18 )
Antimicrobial Peptides (AMPs), within their realm incorporate a diverse group of structurally and functionally varied peptides, playing crucial roles in innate immunity. Over the last few decades, the field of AMP has seen a huge upsurge, mainly owing to the generation of the so-called drug resistant ‘superbugs’ as well as limitations associated with the existing antimicrobial agents. Due to their resilient biological properties, AMPs can very well form the sustainable alternative for nextgeneration therapeutic agents. Certain drawbacks associated with existing AMPs are, however, issues of major concern, circumventing which are imperative. These limitations mainly include proteolytic cleavage and hence poor stability inside the biological systems, reduced activity due to inadequate interaction with the microbial membrane, and ineffectiveness because of inappropriate delivery among others. In this context, the application of naturally occurring AMPs as an efficient prototype for generating various synthetic and designed counterparts has evolved as a new avenue in peptide-based therapy. Such designing approaches help to overcome the drawbacks of the parent AMPs while retaining the inherent activity. In this review, we summarize some of the basic NMR structure based approaches and techniques which aid in improving the activity of AMPs, using the example of a 16-residue dengue virus fusion protein derived peptide, VG16KRKP. Using first principle based designing technique and high resolution NMR-based structure characterization we validate different types of modifications of VG16KRKP, highlighting key motifs, which optimize its activity. The approaches and designing techniques presented can support our peers in their drug development work.
Antimicrobial peptides, superbugs, de novo peptide designing, NMR spectroscopy, trNOESY, VG16KRKP.
Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII(M), Kolkata 700054, Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII(M), Kolkata 700054, Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII(M), Kolkata 700054, Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII(M), Kolkata 700054