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 Mr (9758) that is synthesized by rat seminal vesicle (SV) epithelium under strict androgen transcriptional control. This protein is of obvious pharmacological interest because it has potent nonspecies-specific immunomodulatory, anti-inflammatory, and pro-coagulant activities. In evaluating the clinical relevance and the possible use in medicine of SV-IV, we became interested in the study of its structure-function relationships and aimed to identify in its polypeptide chain specific peptide fragments possessing the marked anti-inflammatory properties of the protein not associated with other biological activities (pro-coagulation and immunomodulation) typical of this molecule. By using two different experimental approaches (the fragmentation of the protein into peptide derivatives by chemical methods and the organic synthesis on solid phase of selected peptide fragments), data were obtained showing that in this protein: (a) the immunomodulatory activity is related to the structural integrity of the whole molecule; (b) the anti-inflammatory activity is located in the N-terminal region of the molecule, the 8-16 peptide fragment being the most active; (c) the identified anti-inflammatory peptide derivatives do not seem to possess pro-coagulant activity, even though this particular function has been located in the 1-70 segment of the molecule.
Ialenti
A
A
Department of Experimental Pharmacology, Faculty of Pharmacy, University of Naples Federico II, Naples, Italy.
Santagada
V
V
Caliendo
G
G
Severino
B
B
Fiorino
F
F
Maffia
P
P
Ianaro
A
A
Morelli
F
F
Di Micco
B
B
Cartenì
M
M
Stiuso
P
P
Metafora
V
V
Metafora
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003029:Coagulants / Q000138:chemical synthesis / Q000737:chemistry; D003488:Cyanogen Bromide / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D029607:Seminal Vesicle Secretory Proteins
D000893:Anti-Inflammatory Agents; D003029:Coagulants; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D011506:Proteins; D029607:Seminal Vesicle Secretory Proteins; C101178:Svs4 protein, rat; D003488:Cyanogen Bromide