Synthesis of novel anti-inflammatory peptides derived from the amino-acid sequence of the bioactive protein SV-IV

SV-IV is a basic, thermostable, secretory protein of low M-r (9758) that is synthesized by rat seminal vesicle (SV) epithelium under strict androgen t ranscriptional control. This protein is of obvious pharmacological interest because it has potent nonspecies-specific immunomodulatory, anti-inflammat ory, and pro-coagulant activities. In evaluating the clinical relevance and the possible use in medicine of SV-IV, we became interested in the study o f its structure-function relationships and aimed to identify in its polypep tide chain specific peptide fragments possessing the marked anti-inflammato ry properties of the protein not associated with other biological activitie s (pro-coagulation and immunomodulation) typical of this molecule. By using two different experimental approaches (the fragmentation of the protein in to peptide derivatives by chemical methods and the organic synthesis on sol id phase of selected peptide fragments), data were obtained showing that in this protein: (a) the immunomodulatory activity is related to the structur al integrity of the whole molecule; (b) the anti-inflammatory activity is l ocated in the N-terminal region of the molecule, the 8-16 peptide fragment being the most active; (c) the identified anti-inflammatory peptide derivat ives do not seem to possess pro-coagulant activity, even though this partic ular function has been located in the 1-70 segment of the molecule.