This project is concerned with the analysis, synthesis, and structure- function relationships of biologically active peptides. The design and synthesis of peptide antigens for immunological studies of the structure-function relationships of angiotensin II (AII) and GnRH receptors, and the antitumor activity of potent magainin analogues, are the focus of our current studies. Based on amino acid sequences deduced from receptor cDNAs, segments from the putative extracellular and cytoplasmic domains were synthesized and conjugated to thyroglobulin. The antisera to such sequences are being analyzed to evaluate their receptor specificity and blocking activity. Suitably characterized antisera will be employed for studies on AII and GnRH receptor distributions in tissues, expression and glycosylation of receptors, and their associated signal transduction mechanisms. Synthetic magainins A and G are highly potent in causing osmotic lysis of bacteria and protozoa. In addition to previously tested hematopoietic and small cell lung cancer cells (SCLC), these two magainin analogues were also tested for growth inhibition on forty tumor cell lines of various types. They were most potent against melanoma, followed by hematopoietic, SCLC non-SCLC, renal, and least active against ovarian, colon and CNS cancer cells. These findings suggest that potent magainin analogues, either alone or in combination with chemotherapeutic agents, may have potential for the development of anticancer drugs. In particular, a therapeutic agent based on a potent magainin analogue is worth exploring for the treatment of melanoma.
