Grafting of antiangiogenic A7R peptide onto disulfide-rich peptide scaffolds, investigation of serum stability and bioactivity

Peptides, which have high therapeutic potential due to their high selectivity to bind to their targets, are drug candidates that have attracted attention especially in recent years. In addition, low toxicity and low immune response make peptides more valuable. Although peptides have high therapeutic potential, their use as drugs is limited due to their poor stability. However, many peptides have been developed to date, inspired by naturally occurring peptides, and their stability and bioactivity have been increased. Therapeutic peptides have various bioactivities such as anticancer and antiangiogenic activity. Angiogenesis is the formation of new blood vessels. Angiogenic peptides prevent tumor growth and angiogenesis by specifically inhibiting the interactions of tumor cells with important signaling proteins that regulate the angiogenesis process. A7R is an antiangiogenic peptide obtained with phage display technology that inhibits tumor growth. It has been reported in the literature that A7R peptide is an ideal biomolecule for tumor imaging and anticancer studies. However, one of the biggest reasons why the A7R peptide cannot be a drug candidate is its low stability. For example, in stability studies conducted with 25% mouse serum, it was reported that the A7R peptide was completely degraded in serum in a short time of two hours. In this thesis study, the A7R peptide with low serum stability was grafted onto peptide scaffolds known to have high stability, thus increasing serum stability.