Synthesis and conformation of a hexapeptide fragment (3-8) of SPF peptide by NMR and restrained molecular dynamics

Abstract

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Seminalplasmin (SPLN) is a 47-residue peptide from bovine seminal plasma which shows broad spectrum antimicrobial activity but no hemolytic activity and it lyses dividing mammalian cells, but not resting cells. It is reported that the 28-40 segment of SPLN, designated as SPF, is the most hydrophobic stretch of SPLN and primarily responsible for the membrane-perturbing activity of SPLN. The SPF peptide has a helical structure as shown by CD analysis. Molecular dynamics studies show that SPF peptide has two helical segments, regions Leu4-Phe7 and Lys10-Ile12. The helical structure makes it biologically active. The hexapeptide studied presently, Leu-Leu-Glu-Thr-Phe-Leu, forms the 3-8 region of SPF. NMR analysis shows that the hexapeptide Leu-Leu-Glu-Thr-Phe-Leu has an extended backbone conformation. Molecular dynamics studies show that the electrostatic attraction between opposite charges at 2^nd and 5^th positions stabilises the helical structure of SPF peptide. The lack of 2^nd residue (Lys) in the experimental 3-8 peptide fragment of SPF explains its extended structure. This information has led to the conclusion that the regions other than this hexapeptide motif are essential to maintain the helical structure of SPF peptide</smarttagtype>