Synthesis and biological activity of lipocortin-5 N-terminus: An attempt to define some structural requirements for activity

We have determined that the peptide lipocortin-5 N-terminus (LIPO-5NT) was able to inhibit rabbit platelet aggregation in a concentration- and time-dependent manner. In order to assess which residues in LIPO-5NT were essential for its activity, an 'Ala-scan' was performed by sequentially substituting alanine for each of the first six residues. We demonstrate that replacement of Gln3 by alanine increases inhibition by about 20 times, while substitution of Leu5 gives an increase in activity of about 70 times.