Synthesis of peptide containing new sulfonamide derivatives

Peptides regulate many biological mechanisms, which make them attractive molecules to become drug active substances. The literature review shows that the sulfonamides and short peptide sequences separately have broad biological activity. It is also known that low molecular weight peptides cross biological barriers more easily and they also less susceptible to protease attacks. However, it has disadvantages such as low bioavailability and poor stability. It is therefore important to replace the peptide moieties with high affinity non-peptide structures. For this purpose, it is aimed to synthesize possible active compounds similar to biological systems by the reaction of dipeptides and sulfonamide derivatives. There is very limited information on this subject in the literature. Within the scope of this thesis, new sulfonamide derivatives containing dipeptide were prepared as summarized in the scheme below. The structures of all new compounds were determined by spectroscopic methods (IR, NMR, MS) and their carbonic anhydrase inhibitory properties were determined against some human carbonic anhydrase enzymes (hCA I, hCA II, hCA IV, hCA IX and hCA XII). The majority of synthesized dipeptides inhibited carbonic anhydrase enzymes at nanomolar levels. However, those containing alanine, phenylalanine, valine, leucine, isoleucine and methionine amino acid exhibited the best carbonic anhydrase enzyme inhibitor properties.